chr20-4857068-T-G

Position:

• chr20-4857068-T-G

Variant summary

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

The NM_005116.6(SLC23A2):​c.1857A>C​(p.Leu619Phe) 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. 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: 32)
• Consequence: SLC23A2 NM_005116.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.220

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]

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=0.14990303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A2	NM_005116.6	c.1857A>C	p.Leu619Phe	missense_variant	17/17	ENST00000338244.6	NP_005107.4
SLC23A2	NM_203327.2	c.1857A>C	p.Leu619Phe	missense_variant	17/17		NP_976072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC23A2	ENST00000338244.6	c.1857A>C	p.Leu619Phe	missense_variant	17/17	1	NM_005116.6	ENSP00000344322.1
SLC23A2	ENST00000379333.5	c.1857A>C	p.Leu619Phe	missense_variant	17/17	1		ENSP00000368637.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 29, 2024

The c.1857A>C (p.L619F) alteration is located in exon 17 (coding exon 15) of the SLC23A2 gene. This alteration results from a A to C substitution at nucleotide position 1857, causing the leucine (L) at amino acid position 619 to be replaced by a phenylalanine (F). 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	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.085
Sift	Benign	0.069	T;T
Sift4G	Uncertain	0.036	D;D
Polyphen		0.0010	B;B
Vest4		0.10
MutPred		0.49		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.13
MPC		0.89
ClinPred		0.57	D
GERP RS		0.62
Varity_R		0.093
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs936125458; hg19: chr20-4837714;