Variant rs2288646 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_020322.3(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
NM_020322.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Variant links:

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]

ASIC3 links:

ASIC3 (HGNC:):

ASIC3 links:

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ACMG classification

Classification made for transcript

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. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC3	NM_004769.4 linkuse as main transcript	c.*71G>A		3_prime_UTR_variant	11/11	ENST00000349064.10	NP_004760.1	Q9UHC3-1A0A090N7X8
ASIC3	NM_020322.3 linkuse as main transcript	c.1608G>A	p.Pro536Pro	synonymous_variant	10/10		NP_064718.1	Q9UHC3-2A0A090N8Z6
ASIC3	NM_020321.3 linkuse as main transcript	c.*37G>A		3_prime_UTR_variant	11/11		NP_064717.1	Q9UHC3-3A0A090N8Q1
ASIC3	NR_046401.1 linkuse as main transcript	n.2113G>A		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC3	ENST00000349064.10 linkuse as main transcript	c.*71G>A		3_prime_UTR_variant	11/11	1	NM_004769.4	ENSP00000344838.5		Q9UHC3-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

179

AN:

152128

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00192

AC XY:

260

AN XY:

135742

show subpopulations

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.:

Cov.:

AF XY:

0.00126

AC XY:

918

AN XY:

727170

show subpopulations

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.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74446

show subpopulations

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.:

Bravo

AF:

0.00130

Asia WGS

AF:

0.0120

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over