rs1776964

Variant names:

• chr20-4899662-G-A
• rs1776964
• NM_005116.6:c.375C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005116.6(SLC23A2):​c.375C>T​(p.Ala125Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,613,436 control chromosomes in the GnomAD database, including 176,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16191 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160637 hom.)
• Consequence: SLC23A2 NM_005116.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 33 publications found

Genes affected

SLC23A2 (HGNC:10973): (solute carrier family 23 member 2) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two required transporters and the encoded protein accounts for tissue-specific uptake of vitamin C. Previously, this gene had an official symbol of SLC23A1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A2	NM_005116.6	c.375C>T	p.Ala125Ala	synonymous_variant	Exon 6 of 17	ENST00000338244.6	NP_005107.4
SLC23A2	NM_203327.2	c.375C>T	p.Ala125Ala	synonymous_variant	Exon 6 of 17		NP_976072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC23A2	ENST00000338244.6	c.375C>T	p.Ala125Ala	synonymous_variant	Exon 6 of 17	1	NM_005116.6	ENSP00000344322.1
SLC23A2	ENST00000379333.5	c.375C>T	p.Ala125Ala	synonymous_variant	Exon 6 of 17	1		ENSP00000368637.1
SLC23A2	ENST00000468355.5	n.741C>T		non_coding_transcript_exon_variant	Exon 6 of 12	1
SLC23A2	ENST00000423430.1	c.-16C>T		upstream_gene_variant		5		ENSP00000396364.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69337 AN: 151824 Hom.: 16178 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.456

GnomAD2 exomes AF: 0.472 AC: 118690 AN: 251436 AF XY: 0.474

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.533

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.466 AC: 681459 AN: 1461494 Hom.: 160637 Cov.: 43 AF XY: 0.468 AC XY: 340608 AN XY: 727092

African (AFR) AF: 0.387 AC: 12965 AN: 33476

American (AMR) AF: 0.436 AC: 19515 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12252 AN: 26126

East Asian (EAS) AF: 0.595 AC: 23602 AN: 39694

South Asian (SAS) AF: 0.476 AC: 41059 AN: 86252

European-Finnish (FIN) AF: 0.566 AC: 30209 AN: 53416

Middle Eastern (MID) AF: 0.487 AC: 2807 AN: 5762

European-Non Finnish (NFE) AF: 0.460 AC: 510814 AN: 1111666

Other (OTH) AF: 0.468 AC: 28236 AN: 60380

GnomAD4 genome AF: 0.457 AC: 69389 AN: 151942 Hom.: 16191 Cov.: 32 AF XY: 0.462 AC XY: 34324 AN XY: 74248

African (AFR) AF: 0.395 AC: 16354 AN: 41422

American (AMR) AF: 0.467 AC: 7132 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1625 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2813 AN: 5130

South Asian (SAS) AF: 0.479 AC: 2308 AN: 4820

European-Finnish (FIN) AF: 0.568 AC: 5996 AN: 10562

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31830 AN: 67946

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.460 Hom.: 13388

Bravo AF: 0.440

Asia WGS AF: 0.492 AC: 1711 AN: 3478

EpiCase AF: 0.459

EpiControl AF: 0.462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-2.7
PromoterAI		0.037	Neutral
Mutation Taster		=98/2	polymorphism (auto)

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: rs1776964; hg19: chr20-4880308; COSMIC: COSV57779965; COSMIC: COSV57779965;