5-139379813-C-T

Variant names:

• chr5-139379813-C-T
• rs33972313
• NM_005847.5:c.790G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152685.4(SLC23A1):​c.802G>A​(p.Val268Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,613,960 control chromosomes in the GnomAD database, including 952 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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: 𝑓 0.039 (159 hom., cov: 32)
  • Exomes 𝑓: 0.031 (793 hom.)
• Consequence: SLC23A1 NM_152685.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 61 publications found

Genes affected

SLC23A1 (HGNC:10974): (solute carrier family 23 member 1) 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 transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032784939).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152685.4. 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
	SLC23A1	NM_005847.5	MANE Select	c.790G>A	p.Val264Met	missense	Exon 8 of 15	NP_005838.3
	SLC23A1	NM_152685.4		c.802G>A	p.Val268Met	missense	Exon 8 of 15	NP_689898.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A1	ENST00000348729.8	TSL:1 MANE Select	c.790G>A	p.Val264Met	missense	Exon 8 of 15	ENSP00000302701.4
	SLC23A1	ENST00000353963.7	TSL:1	c.802G>A	p.Val268Met	missense	Exon 8 of 15	ENSP00000302851.5
	SLC23A1	ENST00000882127.1		c.790G>A	p.Val264Met	missense	Exon 9 of 16	ENSP00000552186.1

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5937 AN: 151984 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0326

GnomAD2 exomes AF: 0.0273 AC: 6863 AN: 251368 AF XY: 0.0265

Gnomad AFR exome AF: 0.0669

Gnomad AMR exome AF: 0.0182

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0219

Gnomad NFE exome AF: 0.0318

Gnomad OTH exome AF: 0.0217

GnomAD4 exome AF: 0.0307 AC: 44905 AN: 1461858 Hom.: 793 Cov.: 34 AF XY: 0.0299 AC XY: 21748 AN XY: 727236

African (AFR) AF: 0.0689 AC: 2307 AN: 33480

American (AMR) AF: 0.0194 AC: 868 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00953 AC: 249 AN: 26136

East Asian (EAS) AF: 0.00962 AC: 382 AN: 39700

South Asian (SAS) AF: 0.0168 AC: 1449 AN: 86258

European-Finnish (FIN) AF: 0.0223 AC: 1192 AN: 53420

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.0329 AC: 36560 AN: 1111978

Other (OTH) AF: 0.0305 AC: 1843 AN: 60396

GnomAD4 genome AF: 0.0391 AC: 5944 AN: 152102 Hom.: 159 Cov.: 32 AF XY: 0.0380 AC XY: 2828 AN XY: 74354

African (AFR) AF: 0.0723 AC: 2999 AN: 41460

American (AMR) AF: 0.0264 AC: 403 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5168

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4820

European-Finnish (FIN) AF: 0.0256 AC: 271 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0295 AC: 2004 AN: 67988

Other (OTH) AF: 0.0327 AC: 69 AN: 2110

Alfa AF: 0.0304 Hom.: 309

Bravo AF: 0.0414

TwinsUK AF: 0.0351 AC: 130

ALSPAC AF: 0.0324 AC: 125

ESP6500AA AF: 0.0649 AC: 286

ESP6500EA AF: 0.0345 AC: 297

ExAC AF: 0.0294 AC: 3566

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.0289

EpiControl AF: 0.0280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.83	D
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.2	T
PhyloP100		1.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.065
Sift	Benign	0.19	T
Sift4G	Benign	0.14	T
Vest4		0.093
MPC		0.82
ClinPred		0.016	T
GERP RS		2.7
gMVP		0.88
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs33972313; hg19: chr5-138715502; COSMIC: COSV62296530; COSMIC: COSV62296530;