rs111706634

Variant names:

• chr2-178456149-C-A
• rs111706634
• NM_001042702.5:c.547C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-178456149-C-A
• chr2-178456149-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP6_Moderate BP7

The NM_001042702.5(PJVK):​c.547C>A​(p.Arg183Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PJVK NM_001042702.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.0005150
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43
• Publications: 17 publications found

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]

PJVK Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 59

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP6: Variant 2-178456149-C-A is Benign according to our data. Variant chr2-178456149-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1683214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042702.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PJVK	NM_001042702.5	MANE Select	c.547C>A	p.Arg183Arg	splice_region synonymous	Exon 4 of 7	NP_001036167.1	Q0ZLH3
	PJVK	NM_001353775.2		c.556C>A	p.Arg186Arg	splice_region synonymous	Exon 4 of 7	NP_001340704.1
	PJVK	NM_001353776.2		c.652C>A	p.Arg218Arg	splice_region synonymous	Exon 4 of 6	NP_001340705.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PJVK	ENST00000644580.2	MANE Select	c.547C>A	p.Arg183Arg	splice_region synonymous	Exon 4 of 7	ENSP00000495855.2	Q0ZLH3
	PJVK	ENST00000375129.8	TSL:1	c.547C>A	p.Arg183Arg	splice_region synonymous	Exon 3 of 6	ENSP00000364271.4	Q0ZLH3
	PJVK	ENST00000437056.5	TSL:1	n.1417C>A		splice_region non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248764 AF XY: 0.00000741

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726958

African (AFR) AF: 0.000388 AC: 13 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111766

Other (OTH) AF: 0.000248 AC: 15 AN: 60374

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		1.4
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00052
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs111706634; hg19: chr2-179320876;