chr4-155854162-A-G

Position:

• chr4-155854162-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017419.3(ASIC5):​c.500T>C​(p.Val167Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ASIC5 NM_017419.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.602

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]

ACMG classification

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=0.04499331).
• BP6: Variant 4-155854162-A-G is Benign according to our data. Variant chr4-155854162-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3318229.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	c.500T>C	p.Val167Ala	missense_variant	3/10	ENST00000537611.3
ASIC5	XM_017008291.2	c.500T>C	p.Val167Ala	missense_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC5	ENST00000537611.3	c.500T>C	p.Val167Ala	missense_variant	3/10	1	NM_017419.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.6
DANN	Benign	0.76
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.97	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.55		Loss of helix (P = 0.079);
MVP		0.014
MPC		0.013
ClinPred		0.048	T
GERP RS		2.4
Varity_R		0.021
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1741462429; hg19: chr4-156775314;