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GeneBe

5-139378327-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005847.5(SLC23A1):c.1204T>G(p.Tyr402Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC23A1
NM_005847.5 missense

Scores

4
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC23A1NM_005847.5 linkuse as main transcriptc.1204T>G p.Tyr402Asp missense_variant 11/15 ENST00000348729.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC23A1ENST00000348729.8 linkuse as main transcriptc.1204T>G p.Tyr402Asp missense_variant 11/151 NM_005847.5 P1Q9UHI7-1
SLC23A1ENST00000353963.7 linkuse as main transcriptc.1216T>G p.Tyr406Asp missense_variant 11/151 Q9UHI7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 03, 2023The c.1216T>G (p.Y406D) alteration is located in exon 11 (coding exon 11) of the SLC23A1 gene. This alteration results from a T to G substitution at nucleotide position 1216, causing the tyrosine (Y) at amino acid position 406 to be replaced by an aspartic acid (D). 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
0.91
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
Cadd
Pathogenic
26
Dann
Uncertain
0.99
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.041
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.9
D;D
REVEL
Uncertain
0.47
Sift
Benign
0.14
T;T
Sift4G
Benign
0.18
T;T
Vest4
0.83
MutPred
0.81
.;Loss of sheet (P = 0.0315);
MVP
0.72
MPC
1.8
ClinPred
0.89
D
GERP RS
5.3
gMVP
0.94

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.

Other links and lift over

hg19: chr5-138714016; API