Variant 20-4869916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005116.6(SLC23A2):c.1240G>A(p.Ala414Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC23A2
NM_005116.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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:

SLC23A2 (HGNC:):

SLC23A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A2	NM_005116.6 linkuse as main transcript	c.1240G>A	p.Ala414Thr	missense_variant	12/17	ENST00000338244.6	NP_005107.4	Q9UGH3-1A0A140VK48
SLC23A2	NM_203327.2 linkuse as main transcript	c.1240G>A	p.Ala414Thr	missense_variant	12/17		NP_976072.1	Q9UGH3-1A0A140VK48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC23A2	ENST00000338244.6 linkuse as main transcript	c.1240G>A	p.Ala414Thr	missense_variant	12/17	1	NM_005116.6	ENSP00000344322.1	Q9UGH3-1
SLC23A2	ENST00000379333.5 linkuse as main transcript	c.1240G>A	p.Ala414Thr	missense_variant	12/17	1		ENSP00000368637.1	Q9UGH3-1
SLC23A2	ENST00000468355.5 linkuse as main transcript	n.1606G>A		non_coding_transcript_exon_variant	12/12	1
SLC23A2	ENST00000423430.1 linkuse as main transcript	c.508G>A	p.Ala170Thr	missense_variant	4/8	5		ENSP00000396364.1	H0Y544

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

128112

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1321964

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

661472

show subpopulations

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:

0.00000101

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

128112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60642

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.1240G>A (p.A414T) alteration is located in exon 12 (coding exon 10) of the SLC23A2 gene. This alteration results from a G to A substitution at nucleotide position 1240, causing the alanine (A) at amino acid position 414 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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;D

Vest4

0.78

MutPred

0.54

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.36

MPC

1.9

ClinPred

0.99

GERP RS

5.5

Varity_R

0.68

gMVP

0.88

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over