12-50058782-G-C

Variant names:

• chr12-50058782-G-C
• rs1191015788
• NM_001095.4:c.16G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001095.4(ASIC1):​c.16G>C​(p.Glu6Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,430,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E6K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ASIC1 NM_001095.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15935361).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001095.4. 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
	ASIC1	NM_001095.4	MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 2 of 12	NP_001086.2
	ASIC1	NM_020039.4		c.16G>C	p.Glu6Gln	missense	Exon 2 of 12	NP_064423.2
	ASIC1	NM_001412756.1		c.16G>C	p.Glu6Gln	missense	Exon 2 of 13	NP_001399685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	ENST00000447966.7	TSL:1 MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 2 of 12	ENSP00000400228.3	P78348-2
	ASIC1	ENST00000228468.8	TSL:1	c.16G>C	p.Glu6Gln	missense	Exon 2 of 12	ENSP00000228468.4	P78348-1
	ASIC1	ENST00000895671.1		c.16G>C	p.Glu6Gln	missense	Exon 2 of 13	ENSP00000565730.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000866 AC: 2 AN: 230820 AF XY: 0.00000809

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000959

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000559 AC: 8 AN: 1430906 Hom.: 0 Cov.: 30 AF XY: 0.00000566 AC XY: 4 AN XY: 707254

African (AFR) AF: 0.00 AC: 0 AN: 32974

American (AMR) AF: 0.00 AC: 0 AN: 43132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24006

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39302

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51986

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5650

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1093378

Other (OTH) AF: 0.00 AC: 0 AN: 59034

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.061
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.11
Sift	Benign	0.13	T
Sift4G	Benign	0.24	T
Polyphen		0.045	B
Vest4		0.23
MutPred		0.20		Gain of helix (P = 0.062)
MVP		0.26
MPC		0.82
ClinPred		0.56	D
GERP RS		3.9
Varity_R		0.24
gMVP		0.44
Mutation Taster		=77/23	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: rs1191015788; hg19: chr12-50452565;