Variant chr4-155829965-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017419.3(ASIC5):c.1409A>G(p.Asn470Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000673 in 1,603,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

ASIC5
NM_017419.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

ASIC5 (HGNC:17537): (acid sensing ion channel subunit family member 5) This gene belongs to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family, members of which have been identified in many animal species ranging from the nematode to human. The amiloride-sensitive Na(+) channel encoded by this gene is primarily expressed in the small intestine, however, its exact function is not known. [provided by RefSeq, Jul 2008]

ASIC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051207304).

BP6

Variant 4-155829965-T-C is Benign according to our data. Variant chr4-155829965-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655152.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC5	NM_017419.3 linkuse as main transcript	c.1409A>G	p.Asn470Ser	missense_variant	10/10	ENST00000537611.3
ASIC5	XM_017008291.2 linkuse as main transcript	c.1283A>G	p.Asn428Ser	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC5	ENST00000537611.3 linkuse as main transcript	c.1409A>G	p.Asn470Ser	missense_variant	10/10	1	NM_017419.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000839

AC:

AN:

238502

Hom.:

AF XY:

0.0000776

AC XY:

AN XY:

128868

show subpopulations

Gnomad AFR exome

AF:

0.000400

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000391

Gnomad SAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000620

AC:

AN:

1451822

Hom.:

Cov.:

AF XY:

0.0000734

AC XY:

AN XY:

721854

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000611

Gnomad4 SAS exome

AF:

0.0000473

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000452

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000118

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ASIC5: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.070

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.69

M_CAP

Benign

0.022

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.77

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.28

MVP

0.16

MPC

0.013

ClinPred

0.012

GERP RS

-5.7

Varity_R

0.050

gMVP

0.50

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over