9-19528120-G-A

Variant names:

• chr9-19528120-G-A
• rs2132659865
• NM_020344.4:c.1498C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020344.4(SLC24A2):​c.1498C>T​(p.Pro500Ser) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P500A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC24A2 NM_020344.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

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.1498C>T	p.Pro500Ser	missense	Exon 9 of 11	NP_065077.1	Q9UI40-1
	SLC24A2	NM_001375850.1		c.1498C>T	p.Pro500Ser	missense	Exon 9 of 11	NP_001362779.1	Q9UI40-1
	SLC24A2	NM_001193288.3		c.1447C>T	p.Pro483Ser	missense	Exon 8 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.1498C>T	p.Pro500Ser	missense	Exon 9 of 11	ENSP00000344801.1	Q9UI40-1
	SLC24A2	ENST00000286344.4	TSL:1	c.1447C>T	p.Pro483Ser	missense	Exon 8 of 10	ENSP00000286344.3	Q9UI40-2
	SLC24A2	ENST00000903169.1		c.1498C>T	p.Pro500Ser	missense	Exon 9 of 11	ENSP00000573228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.54
Sift	Benign	0.11	T
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.71
MutPred		0.36		Loss of ubiquitination at K497 (P = 0.079)
MVP		0.97
MPC		0.13
ClinPred		0.96	D
GERP RS		6.2
Varity_R		0.40
gMVP		0.93
Mutation Taster		=32/68	disease causing

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: rs2132659865; hg19: chr9-19528118;