ENST00000357922.8:c.1608G>A

Variant names:

• chr7-151052723-G-A
• rs2288646
• ENST00000357922.8:c.1608G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The ENST00000357922.8(ASIC3):​c.1608G>A​(p.Pro536Pro) 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357922.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	NM_004769.4	MANE Select	c.*71G>A		3_prime_UTR	Exon 11 of 11	NP_004760.1
	ASIC3	NM_020322.3		c.1608G>A	p.Pro536Pro	synonymous	Exon 10 of 10	NP_064718.1
	ASIC3	NR_046401.1		n.2113G>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	ENST00000357922.8	TSL:1	c.1608G>A	p.Pro536Pro	synonymous	Exon 10 of 10	ENSP00000350600.4
	ASIC3	ENST00000468325.5	TSL:1	n.*295G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000418605.1
	ASIC3	ENST00000349064.10	TSL:1 MANE Select	c.*71G>A		3_prime_UTR	Exon 11 of 11	ENSP00000344838.5

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

GnomAD2 exomes AF: 0.00205 AC: 514 AN: 251198 AF XY: 0.00192

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.000268 AC: 12 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0425 AC: 1688 AN: 39698

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1111910

Other (OTH) AF: 0.00136 AC: 82 AN: 60384

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

African (AFR) AF: 0.000481 AC: 20 AN: 41544

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.3
DANN	Benign	0.88
PhyloP100		-2.0
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

Other links and lift over

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