Genetic Variant SLC23A2:p.Leu384Val (chr20-4870006-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_005116.6(SLC23A2):c.1150C>G(p.Leu384Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC23A2
NM_005116.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Variant links:

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]

SLC23A2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A2	NM_005116.6 link	c.1150C>G	p.Leu384Val	missense_variant	Exon 12 of 17	ENST00000338244.6	NP_005107.4	Q9UGH3-1A0A140VK48
SLC23A2	NM_203327.2 link	c.1150C>G	p.Leu384Val	missense_variant	Exon 12 of 17		NP_976072.1	Q9UGH3-1A0A140VK48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC23A2	ENST00000338244.6 link	c.1150C>G	p.Leu384Val	missense_variant	Exon 12 of 17	1	NM_005116.6	ENSP00000344322.1	Q9UGH3-1
SLC23A2	ENST00000379333.5 link	c.1150C>G	p.Leu384Val	missense_variant	Exon 12 of 17	1		ENSP00000368637.1	Q9UGH3-1
SLC23A2	ENST00000468355.5 link	n.1516C>G		non_coding_transcript_exon_variant	Exon 12 of 12	1
SLC23A2	ENST00000423430.1 link	c.418C>G	p.Leu140Val	missense_variant	Exon 4 of 8	5		ENSP00000396364.1	H0Y544

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250414

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461066

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1150C>G (p.L384V) alteration is located in exon 12 (coding exon 10) of the SLC23A2 gene. This alteration results from a C to G substitution at nucleotide position 1150, causing the leucine (L) at amino acid position 384 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.072

T;T

Polyphen

0.067

B;B

Vest4

0.64

MutPred

0.52

Gain of glycosylation at S385 (P = 0.0738);Gain of glycosylation at S385 (P = 0.0738);

MVP

0.043

MPC

1.2

ClinPred

0.21

GERP RS

5.5

Varity_R

0.45

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over