5-139378291-C-G

Variant names:

• chr5-139378291-C-G
• NM_005847.5:c.1240G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005847.5(SLC23A1):​c.1240G>C​(p.Gly414Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/19 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A1	NM_005847.5	c.1240G>C	p.Gly414Arg	missense_variant	Exon 11 of 15	ENST00000348729.8	NP_005838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8	c.1240G>C	p.Gly414Arg	missense_variant	Exon 11 of 15	1	NM_005847.5	ENSP00000302701.4
SLC23A1	ENST00000353963.7	c.1252G>C	p.Gly418Arg	missense_variant	Exon 11 of 15	1		ENSP00000302851.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445418 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 717630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	31
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.49	T
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.1	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Vest4		0.97
MutPred		0.90		.;Gain of MoRF binding (P = 0.0408);
MVP		0.81
MPC		2.0
ClinPred		1.0	D
GERP RS		5.3
gMVP		0.97

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: chr5-138713980;