2-178453333-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001369912.1(PJVK):​c.-77C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,438,228 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00056 ( 7 hom. )

Consequence

PJVK
NM_001369912.1 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.365
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 2-178453333-C-T is Benign according to our data. Variant chr2-178453333-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00546 (831/152272) while in subpopulation AFR AF= 0.0192 (798/41546). AF 95% confidence interval is 0.0181. There are 10 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PJVKNM_001042702.5 linkc.-22-55C>T intron_variant Intron 1 of 6 ENST00000644580.2 NP_001036167.1 Q0ZLH3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PJVKENST00000644580.2 linkc.-22-55C>T intron_variant Intron 1 of 6 NM_001042702.5 ENSP00000495855.2 Q0ZLH3

Frequencies

GnomAD3 genomes
AF:
0.00544
AC:
827
AN:
152154
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0192
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00111
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.000559
AC:
719
AN:
1285956
Hom.:
7
Cov.:
18
AF XY:
0.000467
AC XY:
303
AN XY:
648238
show subpopulations
Gnomad4 AFR exome
AF:
0.0202
Gnomad4 AMR exome
AF:
0.000950
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000621
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000146
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
AF:
0.00546
AC:
831
AN:
152272
Hom.:
10
Cov.:
33
AF XY:
0.00536
AC XY:
399
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0192
Gnomad4 AMR
AF:
0.00111
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00354
Hom.:
1
Bravo
AF:
0.00662
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 12, 2019
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
9.3
DANN
Benign
0.78

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: rs77758075; hg19: chr2-179318060; API