5-139372149-T-G

Position:

• chr5-139372149-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005847.5(SLC23A1):​c.1654A>C​(p.Ile552Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.938

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07518563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A1	NM_005847.5	c.1654A>C	p.Ile552Leu	missense_variant	14/15	ENST00000348729.8	NP_005838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8	c.1654A>C	p.Ile552Leu	missense_variant	14/15	1	NM_005847.5	ENSP00000302701.4
SLC23A1	ENST00000353963.7	c.1666A>C	p.Ile556Leu	missense_variant	14/15	1		ENSP00000302851.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Dec 07, 2024

The c.1666A>C (p.I556L) alteration is located in exon 14 (coding exon 14) of the SLC23A1 gene. This alteration results from a A to C substitution at nucleotide position 1666, causing the isoleucine (I) at amino acid position 556 to be replaced by a leucine (L). 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	0.061
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.63
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.080	N;N
REVEL	Benign	0.043
Sift	Benign	0.75	T;T
Sift4G	Benign	0.80	T;T
Vest4		0.15
MutPred		0.43		.;Loss of ubiquitination at K554 (P = 0.0877);
MVP		0.26
MPC		0.11
ClinPred		0.048	T
GERP RS		2.3
gMVP		0.46

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: chr5-138707838;