rs200391606

Variant names:

• chr7-151048910-G-A
• rs200391606
• NM_004769.4:c.25G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004769.4(ASIC3):​c.25G>A​(p.Glu9Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,559,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: ASIC3 NM_004769.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15502241).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004769.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	NM_004769.4	MANE Select	c.25G>A	p.Glu9Lys	missense	Exon 1 of 11	NP_004760.1	Q9UHC3-1
	ASIC3	NM_020321.3		c.25G>A	p.Glu9Lys	missense	Exon 1 of 11	NP_064717.1	Q9UHC3-3
	ASIC3	NM_020322.3		c.25G>A	p.Glu9Lys	missense	Exon 1 of 10	NP_064718.1	Q9UHC3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC3	ENST00000349064.10	TSL:1 MANE Select	c.25G>A	p.Glu9Lys	missense	Exon 1 of 11	ENSP00000344838.5	Q9UHC3-1
	ASIC3	ENST00000297512.12	TSL:1	c.25G>A	p.Glu9Lys	missense	Exon 1 of 11	ENSP00000297512.8	Q9UHC3-3
	ASIC3	ENST00000357922.8	TSL:1	c.25G>A	p.Glu9Lys	missense	Exon 1 of 10	ENSP00000350600.4	Q9UHC3-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000143 AC: 3 AN: 210154 AF XY: 0.0000179

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000316

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000263 AC: 37 AN: 1406824 Hom.: 0 Cov.: 31 AF XY: 0.0000202 AC XY: 14 AN XY: 691732

African (AFR) AF: 0.00 AC: 0 AN: 32554

American (AMR) AF: 0.00 AC: 0 AN: 41268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22408

East Asian (EAS) AF: 0.00 AC: 0 AN: 39130

South Asian (SAS) AF: 0.00 AC: 0 AN: 76932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 0.0000342 AC: 37 AN: 1080662

Other (OTH) AF: 0.00 AC: 0 AN: 58036

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152374 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74518

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.045
Eigen_PC	Benign	0.0099
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.047	D
Polyphen		0.046	B
Vest4		0.27
MVP		0.80
MPC		0.23
ClinPred		0.66	D
GERP RS		4.0
PromoterAI		0.013	Neutral
Varity_R		0.20
gMVP		0.39
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs200391606; hg19: chr7-150745997;