rs573961700

Variant names:

• chr9-19550148-C-T
• rs573961700
• NM_020344.4:c.1468G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-19550148-C-T
• chr9-19550148-C-A
• chr9-19550148-C-G

Variant summary

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

The NM_020344.4(SLC24A2):​c.1468G>A​(p.Val490Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: SLC24A2 NM_020344.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.70
• Publications: 0 publications found

Genes affected

SLC24A2 (HGNC:10976): (solute carrier family 24 member 2) This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

LOC105375988 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020344.4. 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
	SLC24A2	NM_020344.4	MANE Select	c.1468G>A	p.Val490Ile	missense	Exon 8 of 11	NP_065077.1	Q9UI40-1
	SLC24A2	NM_001375850.1		c.1468G>A	p.Val490Ile	missense	Exon 8 of 11	NP_001362779.1	Q9UI40-1
	SLC24A2	NM_001193288.3		c.1417G>A	p.Val473Ile	missense	Exon 7 of 10	NP_001180217.1	Q9UI40-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A2	ENST00000341998.7	TSL:1 MANE Select	c.1468G>A	p.Val490Ile	missense	Exon 8 of 11	ENSP00000344801.1	Q9UI40-1
	SLC24A2	ENST00000286344.4	TSL:1	c.1417G>A	p.Val473Ile	missense	Exon 7 of 10	ENSP00000286344.3	Q9UI40-2
	SLC24A2	ENST00000903169.1		c.1468G>A	p.Val490Ile	missense	Exon 8 of 11	ENSP00000573228.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152042 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.000955

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251482 AF XY: 0.0000589

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461702 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727174

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000291 AC: 13 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111892

Other (OTH) AF: 0.0000497 AC: 3 AN: 60380

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41514

American (AMR) AF: 0.000393 AC: 6 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		6.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.41		Gain of ubiquitination at K492 (P = 0.2244)
MVP		0.92
MPC		0.43
ClinPred		0.61	D
GERP RS		5.4
Varity_R		0.17
gMVP		0.80
Mutation Taster		=69/31	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: rs573961700; hg19: chr9-19550146; COSMIC: COSV99646841;