5-139378019-G-A

Variant names:

• chr5-139378019-G-A
• rs116659253
• NM_005847.5:c.1409C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005847.5(SLC23A1):​c.1409C>T​(p.Thr470Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.758
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02910313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005847.5. 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.1409C>T	p.Thr470Met	missense	Exon 12 of 15	NP_005838.3
	SLC23A1	NM_152685.4		c.1421C>T	p.Thr474Met	missense	Exon 12 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.1409C>T	p.Thr470Met	missense	Exon 12 of 15	ENSP00000302701.4	Q9UHI7-1
	SLC23A1	ENST00000353963.7	TSL:1	c.1421C>T	p.Thr474Met	missense	Exon 12 of 15	ENSP00000302851.5	Q9UHI7-2
	SLC23A1	ENST00000882127.1		c.1409C>T	p.Thr470Met	missense	Exon 13 of 16	ENSP00000552186.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000136 AC: 34 AN: 250742 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1461654 Hom.: 0 Cov.: 33 AF XY: 0.0000344 AC XY: 25 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111920

Other (OTH) AF: 0.0000662 AC: 4 AN: 60392

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.56	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.76
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Benign	0.16	T
Sift4G	Benign	0.16	T
Vest4		0.28
MVP		0.48
MPC		0.13
ClinPred		0.060	T
GERP RS		1.5
gMVP		0.70
Mutation Taster		=75/25	polymorphism

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: rs116659253; hg19: chr5-138713708; COSMIC: COSV99049708; COSMIC: COSV99049708;