rs377275979

Variant names:

• chr2-178461056-C-A
• NM_001042702.5:c.841C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-178461056-C-A
• chr2-178461056-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042702.5(PJVK):​c.841C>A​(p.Pro281Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PJVK NM_001042702.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21468979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PJVK	NM_001042702.5	c.841C>A	p.Pro281Thr	missense_variant	Exon 7 of 7	ENST00000644580.2	NP_001036167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PJVK	ENST00000644580.2	c.841C>A	p.Pro281Thr	missense_variant	Exon 7 of 7		NM_001042702.5	ENSP00000495855.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T;.;T;.;.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0080
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	.;.;.;.;.;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	.;N;.;N;.;.;.;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	.;.;.;D;.;.;.;D
REVEL	Benign	0.050
Sift	Uncertain	0.020	.;.;.;D;.;.;.;D
Sift4G	Benign	0.12	.;.;.;T;.;.;.;T
Polyphen		0.018	.;B;.;B;.;.;.;B
Vest4		0.11, 0.21
MutPred		0.38		.;Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);.;.;.;Gain of helix (P = 0.0496);
MVP		0.18
MPC		0.12
ClinPred		0.71	D
GERP RS		4.2
Varity_R		0.19
gMVP		0.55

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: chr2-179325783;