chr20-19280979-G-A

Position:

• chr20-19280979-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020689.4(SLC24A3):​c.163G>A​(p.Val55Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,613,002 control chromosomes in the GnomAD database, including 150,187 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.41 (13108 hom., cov: 31)
  • Exomes 𝑓: 0.43 (137079 hom.)
• Consequence: SLC24A3 NM_020689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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]

SLC24A3-AS1 (HGNC:40540): (SLC24A3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0514075E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A3	NM_020689.4	c.163G>A	p.Val55Ile	missense_variant	2/17	ENST00000328041.11	NP_065740.2
SLC24A3-AS1	NR_024564.1	n.529+2160C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A3	ENST00000328041.11	c.163G>A	p.Val55Ile	missense_variant	2/17	1	NM_020689.4	ENSP00000333519.5
SLC24A3-AS1	ENST00000319682.2	n.529+2160C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61977 AN: 151774 Hom.: 13103 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.440 AC: 110152 AN: 250206 Hom.: 24944 AF XY: 0.440 AC XY: 59562 AN XY: 135232

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.501

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.454

GnomAD4 exome AF: 0.430 AC: 628491 AN: 1461110 Hom.: 137079 Cov.: 50 AF XY: 0.430 AC XY: 312843 AN XY: 726796

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.408 AC: 62024 AN: 151892 Hom.: 13108 Cov.: 31 AF XY: 0.409 AC XY: 30382 AN XY: 74234

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.448

Alfa AF: 0.436 Hom.: 34537

Bravo AF: 0.423

TwinsUK AF: 0.442 AC: 1640

ALSPAC AF: 0.420 AC: 1620

ESP6500AA AF: 0.327 AC: 1440

ESP6500EA AF: 0.433 AC: 3725

ExAC AF: 0.434 AC: 52743

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Uncertain	0.97
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.15	.;T
MetaRNN	Benign	0.00011	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.14	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.10	N;.
REVEL	Benign	0.085
Sift	Benign	0.64	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.0	B;B
Vest4		0.043
MPC		0.40
ClinPred		0.0031	T
GERP RS		1.9
Varity_R		0.038
gMVP		0.22

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: rs1569767; hg19: chr20-19261623; COSMIC: COSV60115097;