1-34785239-G-T

Variant names:

• chr1-34785239-G-T
• NM_024009.3:c.477G>T
• GJB3 p.Pro159Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024009.3(GJB3):​c.477G>T​(p.Pro159Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P159P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GJB3 NM_024009.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.55
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-5.55 with no splicing effect.

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.477G>T	p.Pro159Pro	synonymous	Exon 2 of 2	NP_076872.1	O75712
	GJB3	NM_001005752.2		c.477G>T	p.Pro159Pro	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.477G>T	p.Pro159Pro	synonymous	Exon 2 of 2	ENSP00000362464.2	O75712
	GJB3	ENST00000373362.3	TSL:1	c.477G>T	p.Pro159Pro	synonymous	Exon 2 of 2	ENSP00000362460.3	O75712
	SMIM12	ENST00000426886.1	TSL:1	n.208-66830C>A		intron	N/A	ENSP00000429902.1	E5RH51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0050
DANN	Benign	0.70
PhyloP100		-5.6
Mutation Taster		=100/0	polymorphism

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

hg19: chr1-35250840;