16-21258785-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001376256.1(CRYM):ā€‹c.941A>Cā€‹(p.Lys314Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CRYM
NM_001376256.1 missense

Scores

1
9
8

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.99
Variant links:
Genes affected
CRYM (HGNC:2418): (crystallin mu) Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-21258785-T-G is Pathogenic according to our data. Variant chr16-21258785-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 16935.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-21258785-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRYMNM_001376256.1 linkuse as main transcriptc.941A>C p.Lys314Thr missense_variant 8/8 ENST00000572914.2
CRYMNM_001888.5 linkuse as main transcriptc.941A>C p.Lys314Thr missense_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRYMENST00000572914.2 linkuse as main transcriptc.941A>C p.Lys314Thr missense_variant 8/82 NM_001376256.1 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461380
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727048
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 40 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Uncertain
0.085
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
0.72
A;A;A;A
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.0
N;N
REVEL
Uncertain
0.51
Sift
Uncertain
0.025
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
0.91
P;P
Vest4
0.25
MutPred
0.82
Loss of ubiquitination at K314 (P = 0.0192);Loss of ubiquitination at K314 (P = 0.0192);
MVP
0.82
MPC
0.73
ClinPred
0.73
D
GERP RS
5.5
Varity_R
0.11
gMVP
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104894512; hg19: chr16-21270106; API