4-155863508-A-G

Position:

chr4-155863508-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_017419.3(ASIC5):c.287T>C(p.Ile96Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000275 in 1,613,776 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ASIC5
NM_017419.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.88

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:

LOC105377507 (HGNC:):

LOC105377507 links:

TDO2 (HGNC:11708): (tryptophan 2,3-dioxygenase) This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]

TDO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008518308).

BP6

Variant 4-155863508-A-G is Benign according to our data. Variant chr4-155863508-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033718.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASIC5	NM_017419.3 linkuse as main transcript	c.287T>C	p.Ile96Thr	missense_variant	2/10	ENST00000537611.3
LOC105377507	XR_001741901.2 linkuse as main transcript	n.211+4610A>G		intron_variant, non_coding_transcript_variant
ASIC5	XM_017008291.2 linkuse as main transcript	c.287T>C	p.Ile96Thr	missense_variant	2/9
LOC105377507	XR_939389.3 linkuse as main transcript	n.4821A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC5	ENST00000537611.3 linkuse as main transcript	c.287T>C	p.Ile96Thr	missense_variant	2/10	1	NM_017419.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000387

AC:

AN:

250890

Hom.:

AF XY:

0.000317

AC XY:

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.000929

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000138

AC:

201

AN:

1461510

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00433

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152266

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00455

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000239

Hom.:

Bravo

AF:

0.00153

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000321

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ASIC5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.67

M_CAP

Benign

0.024

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.27

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0080

Polyphen

0.012

Vest4

0.53

MVP

0.47

MPC

0.048

ClinPred

0.057

GERP RS

4.3

Varity_R

0.25

gMVP

0.64

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