chr9-19576927-C-G

Variant names:

• chr9-19576927-C-G
• rs753004230
• NM_020344.4:c.1225G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020344.4(SLC24A2):​c.1225G>C​(p.Val409Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. V409M) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC24A2 NM_020344.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.787

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092128456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A2	NM_020344.4	c.1225G>C	p.Val409Leu	missense_variant	Exon 6 of 11	ENST00000341998.7	NP_065077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A2	ENST00000341998.7	c.1225G>C	p.Val409Leu	missense_variant	Exon 6 of 11	1	NM_020344.4	ENSP00000344801.1
SLC24A2	ENST00000286344.4	c.1174G>C	p.Val392Leu	missense_variant	Exon 5 of 10	1		ENSP00000286344.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.15
Sift	Benign	0.16	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0020	B;B
Vest4		0.097
MutPred		0.13		Loss of methylation at K411 (P = 0.0822);.;
MVP		0.78
MPC		0.10
ClinPred		0.086	T
GERP RS		4.0
Varity_R		0.056
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs753004230; hg19: chr9-19576925;