NM_005116.6:c.1297G>T

Variant names:

• chr20-4867829-C-A
• NM_005116.6:c.1297G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005116.6(SLC23A2):​c.1297G>T​(p.Gly433Cys) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 31)
• Consequence: SLC23A2 NM_005116.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.986

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.1297G>T	p.Gly433Cys	missense	Exon 13 of 17	NP_005107.4
	SLC23A2	NM_203327.2		c.1297G>T	p.Gly433Cys	missense	Exon 13 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.1297G>T	p.Gly433Cys	missense	Exon 13 of 17	ENSP00000344322.1	Q9UGH3-1
	SLC23A2	ENST00000379333.5	TSL:1	c.1297G>T	p.Gly433Cys	missense	Exon 13 of 17	ENSP00000368637.1	Q9UGH3-1
	SLC23A2	ENST00000877970.1		c.1411G>T	p.Gly471Cys	missense	Exon 15 of 19	ENSP00000548029.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.5
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.97		Loss of disorder (P = 0.0351)
MVP		0.74
MPC		2.0
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.92
gMVP		0.99
Mutation Taster		=5/95	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr20-4848475;