20-4857068-T-G

Variant names:

• chr20-4857068-T-G
• rs936125458
• NM_005116.6:c.1857A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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: SLC23A2 NM_005116.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.220
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14990303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005116.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A2	NM_005116.6	MANE Select	c.1857A>C	p.Leu619Phe	missense	Exon 17 of 17	NP_005107.4
	SLC23A2	NM_203327.2		c.1857A>C	p.Leu619Phe	missense	Exon 17 of 17	NP_976072.1	Q9UGH3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A2	ENST00000338244.6	TSL:1 MANE Select	c.1857A>C	p.Leu619Phe	missense	Exon 17 of 17	ENSP00000344322.1	Q9UGH3-1
	SLC23A2	ENST00000379333.5	TSL:1	c.1857A>C	p.Leu619Phe	missense	Exon 17 of 17	ENSP00000368637.1	Q9UGH3-1
	SLC23A2	ENST00000877970.1		c.1971A>C	p.Leu657Phe	missense	Exon 19 of 19	ENSP00000548029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.22
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.085
Sift	Benign	0.069	T
Sift4G	Uncertain	0.036	D
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.49		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
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs936125458; hg19: chr20-4837714;