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GeneBe

2-178453458-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001042702.5(PJVK):c.49G>A(p.Gly17Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PJVK
NM_001042702.5 missense

Scores

9
1
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PJVKNM_001042702.5 linkuse as main transcriptc.49G>A p.Gly17Arg missense_variant 2/7 ENST00000644580.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PJVKENST00000644580.2 linkuse as main transcriptc.49G>A p.Gly17Arg missense_variant 2/7 NM_001042702.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461810
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 25, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.73
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
Cadd
Pathogenic
26
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.30
T;T;.;T
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.047
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.0
M;M;.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.83
D
Polyphen
1.0
D;D;.;D
Vest4
0.85, 0.78
MutPred
0.90
Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);Gain of MoRF binding (P = 0.036);
MVP
0.37
MPC
0.57
ClinPred
1.0
D
GERP RS
6.1
Varity_R
0.81
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: -27

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: rs886043614; hg19: chr2-179318185; API