rs41310442

Variant names:

• chr1-34785119-C-T
• rs41310442
• NM_024009.3:c.357C>T
• GJB3 p.Asn119Asn

Your query was ambiguous. Multiple possible variants found:

• chr1-34785119-C-T
• chr1-34785119-C-A
• chr1-34785119-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024009.3(GJB3):​c.357C>T​(p.Asn119Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,614,062 control chromosomes in the GnomAD database, including 3,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (467 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3220 hom.)
• Consequence: GJB3 NM_024009.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.03
• Publications: 20 publications found

Genes affected

GJB3 (HGNC:4285): (gap junction protein beta 3) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene can cause non-syndromic deafness or erythrokeratodermia variabilis, a skin disorder. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-34785119-C-T is Benign according to our data. Variant chr1-34785119-C-T is described in ClinVar as Benign. ClinVar VariationId is 46084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024009.3. 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
	GJB3	NM_024009.3	MANE Select	c.357C>T	p.Asn119Asn	synonymous	Exon 2 of 2	NP_076872.1	O75712
	GJB3	NM_001005752.2		c.357C>T	p.Asn119Asn	synonymous	Exon 2 of 2	NP_001005752.1	O75712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB3	ENST00000373366.3	TSL:1 MANE Select	c.357C>T	p.Asn119Asn	synonymous	Exon 2 of 2	ENSP00000362464.2	O75712
	GJB3	ENST00000373362.3	TSL:1	c.357C>T	p.Asn119Asn	synonymous	Exon 2 of 2	ENSP00000362460.3	O75712
	SMIM12	ENST00000426886.1	TSL:1	n.208-66710G>A		intron	N/A	ENSP00000429902.1	E5RH51

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10661 AN: 152118 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0594

GnomAD2 exomes AF: 0.0739 AC: 18506 AN: 250572 AF XY: 0.0751

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.0544

Gnomad EAS exome AF: 0.113

Gnomad FIN exome AF: 0.0721

Gnomad NFE exome AF: 0.0531

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0601 AC: 87784 AN: 1461826 Hom.: 3220 Cov.: 34 AF XY: 0.0621 AC XY: 45163 AN XY: 727218

African (AFR) AF: 0.105 AC: 3510 AN: 33480

American (AMR) AF: 0.0589 AC: 2634 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0538 AC: 1407 AN: 26136

East Asian (EAS) AF: 0.0899 AC: 3569 AN: 39700

South Asian (SAS) AF: 0.133 AC: 11456 AN: 86258

European-Finnish (FIN) AF: 0.0678 AC: 3617 AN: 53366

Middle Eastern (MID) AF: 0.0695 AC: 401 AN: 5768

European-Non Finnish (NFE) AF: 0.0515 AC: 57275 AN: 1112000

Other (OTH) AF: 0.0648 AC: 3915 AN: 60394

GnomAD4 genome AF: 0.0701 AC: 10673 AN: 152236 Hom.: 467 Cov.: 32 AF XY: 0.0716 AC XY: 5328 AN XY: 74438

African (AFR) AF: 0.0987 AC: 4098 AN: 41530

American (AMR) AF: 0.0444 AC: 679 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5178

South Asian (SAS) AF: 0.146 AC: 702 AN: 4818

European-Finnish (FIN) AF: 0.0725 AC: 768 AN: 10600

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3510 AN: 68018

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0586 Hom.: 635

Bravo AF: 0.0684

Asia WGS AF: 0.110 AC: 381 AN: 3478

EpiCase AF: 0.0511

EpiControl AF: 0.0510

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Erythrokeratodermia variabilis et progressiva 1 (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 2B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.5
DANN	Benign	0.87
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41310442; hg19: chr1-35250720;