5-139380843-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005847.5(SLC23A1):c.352G>A(p.Ala118Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,393,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3523394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC23A1	NM_005847.5	c.352G>A	p.Ala118Thr	missense_variant	4/15	ENST00000348729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC23A1	ENST00000348729.8	c.352G>A	p.Ala118Thr	missense_variant	4/15	1	NM_005847.5	P1
SLC23A1	ENST00000353963.7	c.352G>A	p.Ala118Thr	missense_variant	4/15	1
SLC23A1	ENST00000502863.1	n.566G>A		non_coding_transcript_exon_variant	2/2	3
SLC23A1	ENST00000503919.1	n.400G>A		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393154 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688448

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 1.00 Hom.: 330

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.352G>A (p.A118T) alteration is located in exon 4 (coding exon 4) of the SLC23A1 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the alanine (A) at amino acid position 118 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
Cadd	Uncertain	25
Dann	Uncertain	0.98
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.79	N;N
REVEL	Benign	0.19
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.46
MutPred		0.66		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.39
MPC		1.1
ClinPred		0.93	D
GERP RS		5.2
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs866636274; hg19: chr5-138716532;