rs61730978
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000261.2(MYOC):c.303A>G(p.Gln101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
MYOC
NM_000261.2 synonymous
NM_000261.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.820
Genes affected
MYOC (HGNC:7610): (myocilin) MYOC encodes the protein myocilin, which is believed to have a role in cytoskeletal function. MYOC is expressed in many occular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
?
Variant 1-171652309-T-C is Benign according to our data. Variant chr1-171652309-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1723167.Status of the report is reviewed_by_expert_panel, 3 stars.
BP7
?
Synonymous conserved (PhyloP=-0.82 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOC | NM_000261.2 | c.303A>G | p.Gln101= | synonymous_variant | 1/3 | ENST00000037502.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOC | ENST00000037502.11 | c.303A>G | p.Gln101= | synonymous_variant | 1/3 | 1 | NM_000261.2 | P1 | |
MYOC | ENST00000638471.1 | c.130+173A>G | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249654Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134900
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1458828Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 725382
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Glaucoma 1, open angle, E Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Glaucoma Variant Curation Expert Panel | Nov 09, 2022 | The c.303A>G variant in MYOC is a synonymous variant (p.Gln101=). The highest minor allele frequency of this variant was in the African/African American population of gnomAD (v2.1.1) = 0.0003608 (9 alleles out of 24,944), which did not meet the PM2_Supporting allele frequency threshold (<= 0.0001) or the BS1 allele frequency threshold (>= 0.001). This variant was not predicted to affect splicing, as assessed with SpliceAI (<= 0.2), with a CADD score (v1.6) = 0.141 which met the <= 10 threshold for BP4, and the GERP score = -3.2 (threshold < 0), indicating a lack of conservation at this site (BP7). This evidence suggests that the variant does not impact MYOC function. There was no functional evidence predicting a damaging or benign impact of this variant on MYOC function. Although a proband with primary open angle glaucoma had been reported carrying this variant, PM2_Supporting was not met, therefore PS4 did not apply. In summary, this variant met the criteria to receive a score of -2 and to be classified as likely benign (likely benign classification range -2 to -6) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v1, 12 Oct 2021): BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at