1-171636338-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_000261.2(MYOC):​c.1102C>G​(p.Gln368Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

MYOC
NM_000261.2 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.44
Variant links:
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]
MYOCOS (HGNC:53429): (myocilin opposite strand)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 7 uncertain in NM_000261.2
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYOCNM_000261.2 linkc.1102C>G p.Gln368Glu missense_variant Exon 3 of 3 ENST00000037502.11 NP_000252.1 Q99972A0A0S2Z421

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYOCENST00000037502.11 linkc.1102C>G p.Gln368Glu missense_variant Exon 3 of 3 1 NM_000261.2 ENSP00000037502.5 Q99972
MYOCOSENST00000637303.1 linkc.235-2292G>C intron_variant Intron 3 of 3 5 ENSP00000490048.1 A0A1B0GUC4
MYOCENST00000638471.1 linkn.*440C>G non_coding_transcript_exon_variant Exon 4 of 4 5 ENSP00000491206.1 A0A1W2PP09
MYOCENST00000638471.1 linkn.*440C>G 3_prime_UTR_variant Exon 4 of 4 5 ENSP00000491206.1 A0A1W2PP09

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.77
D
MetaSVM
Uncertain
0.085
D
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.46
Sift
Benign
0.20
T
Sift4G
Uncertain
0.050
T
Polyphen
0.98
D
Vest4
0.47
MutPred
0.55
Gain of relative solvent accessibility (P = 0.0999);
MVP
0.96
MPC
0.56
ClinPred
0.91
D
GERP RS
4.5
Varity_R
0.44
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-171605478; API