Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000261.2(MYOC):c.39T>G (p.Pro13=)

CA1244342

293724 (ClinVar)

Gene: MYOC (HGNC:4653)

Condition: open-angle glaucoma (MONDO:0005338)

Inheritance Mode: Autosomal dominant inheritance

UUID: 795036f1-b135-4d5a-9011-ac67bf704e4f

Approved on: 2025-10-09

Published on: 2025-10-09

HGVS expressions

NM_000261.2(MYOC):c.39T>G (p.Pro13=)

NM_000261.2:c.39T>G

NC_000001.11:g.171652573A>C

CM000663.2:g.171652573A>C

NC_000001.10:g.171621713A>C

CM000663.1:g.171621713A>C

NC_000001.9:g.169888336A>C

NG_008859.1:g.5061T>G

ENST00000037502.11:c.39T>G

ENST00000638471.1:c.39T>G

ENST00000037502.10:c.39T>G

ENST00000614688.1:c.39T>G

NM_000261.1:c.39T>G

Benign

BP4 BP7 BA1

PM2 PM4 PM5 BS3 BS1 PS2 PS1 PS3 PS4 PP1 PP3

Evidence Links 0

Expert Panel

Glaucoma VCEP

Criteria Specification Information

Criteria Specification: ClinGen Glaucoma Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYOC Version 2.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Glaucoma VCEP

The c.39T>G variant in MYOC is a synonymous variant (p.Pro13=). The highest minor allele frequency of this variant was in the African/African-American genetic ancestry group of gnomAD (v4.1.0) = 0.07326, which met the ≥ 0.01 threshold set for BA1 (5,497 alleles out of 75032, meeting the threshold of ≥ 5 of at least 2,000 observed alleles). The SpliceAI score = 0, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function. This synonymous variant meets BP4, so BP7 is met. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. As BA1 was met, PP1 did not apply and segregations were not counted. Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant was classified as benign (BA1 is a stand-alone criterion for a benign level of pathogenicity) for juvenile open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.0.0, 5 Dec 2024): BA1, BP4, BP7

BP4

The SpliceAI score = 0, which met the ≤ 0.1 threshold for BP4, suggesting that the variant does not impact MYOC function.

BP7

This synonymous variant meets BP4, so BP7 is met.

BA1

The highest minor allele frequency of this variant was in the African/African-American genetic ancestry group of gnomAD (v4.1.0) = 0.07326, which met the ≥ 0.01 threshold set for BA1 (5,497 alleles out of 75032, meeting the threshold of ≥ 5 of at least 2,000 observed alleles).

PM2

This criterion was not met as BA1 has been met.

PM4

This variant does not cause a protein length change.

PM5

This is not a missense variant.

BS3

No functional evidence has been found for this variant.

BS1

This criterion was not met as BA1 has been met.

PS2

This variant has not been identified de novo.

PS1

This variant does not involve an amino acid change.

PS3

No functional evidence has been found for this variant.

PS4

Although probands with juvenile or primary open angle glaucoma have been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply.

PP1

As BA1 was met, PP1 did not apply and segregations were not counted.

PP3

This is not a missense variant.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.