Variant chr12-50058822-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001095.4(ASIC1):c.56A>C(p.Gln19Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,454,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ASIC1
NM_001095.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21

Variant links:

Genes affected

ASIC1 (HGNC:100): (acid sensing ion channel subunit 1) This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ASIC1 links:

ASIC1 (HGNC:):

ASIC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	2/12	ENST00000447966.7	NP_001086.2	P78348-2A8K1U5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASIC1	ENST00000447966.7 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	2/12	1	NM_001095.4	ENSP00000400228.3	P78348-2
ASIC1	ENST00000228468.8 linkuse as main transcript	c.56A>C	p.Gln19Pro	missense_variant	2/12	1		ENSP00000228468.4	P78348-1
ASIC1	ENST00000550558.5 linkuse as main transcript	n.56A>C		non_coding_transcript_exon_variant	2/13	2		ENSP00000448263.1	F8VSK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

248994

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134498

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1454724

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

722196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000940

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.56A>C (p.Q19P) alteration is located in exon 2 (coding exon 1) of the ASIC1 gene. This alteration results from a A to C substitution at nucleotide position 56, causing the glutamine (Q) at amino acid position 19 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

.;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

D;D

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

N;N

REVEL

Uncertain

0.43

Sift

Benign

0.15

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.59

P;B

Vest4

0.79

MutPred

0.41

Gain of glycosylation at S17 (P = 0.0655);Gain of glycosylation at S17 (P = 0.0655);

MVP

0.26

MPC

1.4

ClinPred

0.64

GERP RS

3.9

Varity_R

0.54

gMVP

0.83

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