chr20-19654103-T-G

Variant names:

• chr20-19654103-T-G
• rs3790279
• NM_020689.4:c.654T>G

Variant summary

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

The NM_020689.4(SLC24A3):​c.654T>G​(p.Ile218Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC24A3 NM_020689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 23 publications found

Genes affected

SLC24A3 (HGNC:10977): (solute carrier family 24 member 3) Plasma membrane sodium/calcium exchangers are an important component of intracellular calcium homeostasis and electrical conduction. Potassium-dependent sodium/calcium exchangers such as SLC24A3 are believed to transport 1 intracellular calcium and 1 potassium ion in exchange for 4 extracellular sodium ions (Kraev et al., 2001 [PubMed 11294880]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020689.4. 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
	SLC24A3	NM_020689.4	MANE Select	c.654T>G	p.Ile218Met	missense	Exon 7 of 17	NP_065740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A3	ENST00000328041.11	TSL:1 MANE Select	c.654T>G	p.Ile218Met	missense	Exon 7 of 17	ENSP00000333519.5
	SLC24A3	ENST00000962751.1		c.579T>G	p.Ile193Met	missense	Exon 6 of 15	ENSP00000632810.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 20051

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.016
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.090	T
Sift4G	Benign	0.085	T
Polyphen		0.20	B
Vest4		0.46
MutPred		0.62		Loss of catalytic residue at I218 (P = 0.0055)
MVP		0.68
MPC		0.62
ClinPred		0.36	T
GERP RS		0.73
Varity_R		0.16
gMVP		0.41
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3790279; hg19: chr20-19634747;