chr5-139379813-C-T

Position:

• chr5-139379813-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005847.5(SLC23A1):​c.790G>A​(p.Val264Met) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (159 hom., cov: 32)
  • Exomes 𝑓: 0.031 (793 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032784939).
• BP6: Variant 5-139379813-C-T is Benign according to our data. Variant chr5-139379813-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A1	NM_005847.5	c.790G>A	p.Val264Met	missense_variant	8/15	ENST00000348729.8	NP_005838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8	c.790G>A	p.Val264Met	missense_variant	8/15	1	NM_005847.5	ENSP00000302701	P1
SLC23A1	ENST00000353963.7	c.802G>A	p.Val268Met	missense_variant	8/15	1		ENSP00000302851
SLC23A1	ENST00000504513.1	c.164+143G>A		intron_variant		5		ENSP00000422688
SLC23A1	ENST00000506512.1	n.401G>A		non_coding_transcript_exon_variant	1/2	4

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

GnomAD3 exomes AF: 0.0273 AC: 6863 AN: 251368 Hom.: 135 AF XY: 0.0265 AC XY: 3595 AN XY: 135854

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 SAS exome AF: 0.0167

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

Gnomad4 AFR exome AF: 0.0689

Gnomad4 AMR exome AF: 0.0194

Gnomad4 ASJ exome AF: 0.00953

Gnomad4 EAS exome AF: 0.00962

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.0223

Gnomad4 NFE exome AF: 0.0329

Gnomad4 OTH exome AF: 0.0305

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

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0279 Hom.: 128

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 v4.3

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;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.065
Sift	Benign	0.19	T;T
Sift4G	Benign	0.14	T;T
Vest4		0.093
MPC		0.82
ClinPred		0.016	T
GERP RS		2.7
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs33972313; hg19: chr5-138715502; COSMIC: COSV62296530; COSMIC: COSV62296530;