rs118203988

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001042702.5(PJVK):​c.161C>T​(p.Thr54Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

PJVK
NM_001042702.5 missense

Scores

8
5
6

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
PJVK (HGNC:29502): (pejvakin) The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59). [provided by RefSeq, Dec 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.956
PP5
Variant 2-178453570-C-T is Pathogenic according to our data. Variant chr2-178453570-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1298.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-178453570-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PJVKNM_001042702.5 linkuse as main transcriptc.161C>T p.Thr54Ile missense_variant 2/7 ENST00000644580.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PJVKENST00000644580.2 linkuse as main transcriptc.161C>T p.Thr54Ile missense_variant 2/7 NM_001042702.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 59 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJul 01, 2006- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.24
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;T;.;T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
.;.;D;D
M_CAP
Benign
0.076
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.6
M;M;.;M
MutationTaster
Benign
1.0
A;A
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-2.3
.;N;.;N
REVEL
Uncertain
0.51
Sift
Benign
0.052
.;T;.;T
Sift4G
Pathogenic
0.0
.;D;.;D
Polyphen
1.0
D;D;.;D
Vest4
0.97, 0.96
MutPred
0.91
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP
0.47
MPC
0.54
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.26
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs118203988; hg19: chr2-179318297; API