rs2288646

chr7-151052723-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The ENST00000357922.8(ASIC3):c.1608G>A(p.Pro536=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,968 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (52 hom.)
• Consequence: ASIC3 ENST00000357922.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

ASIC3 (HGNC:101): (acid sensing ion channel subunit 3) This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, two hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is an acid sensor and may play an important role in the detection of lasting pH changes. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 2 has been observed as proton-gated channels sensitive to gadolinium. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00117 (178/152246) while in subpopulation EAS AF= 0.0264 (137/5184). AF 95% confidence interval is 0.0228. There are 2 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC3	NM_004769.4	c.*71G>A		3_prime_UTR_variant	11/11	ENST00000349064.10
ASIC3	NM_020322.3	c.1608G>A	p.Pro536=	synonymous_variant	10/10
ASIC3	NM_020321.3	c.*37G>A		3_prime_UTR_variant	11/11
ASIC3	NR_046401.1	n.2113G>A		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC3	ENST00000349064.10	c.*71G>A		3_prime_UTR_variant	11/11	1	NM_004769.4	P1

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 152128 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00205 AC: 514 AN: 251198 Hom.: 9 AF XY: 0.00192 AC XY: 260 AN XY: 135742

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0255

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00133 AC: 1947 AN: 1461722 Hom.: 52 Cov.: 34 AF XY: 0.00126 AC XY: 918 AN XY: 727170

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0425

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00117 AC: 178 AN: 152246 Hom.: 2 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74446

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000261 Hom.: 0

Bravo AF: 0.00130

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	3.3
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs2288646; hg19: chr7-150749810; COSMIC: COSV52520533; COSMIC: COSV52520533;