NM_005847.5:c.1051C>G

Variant names:

• chr5-139379229-G-C
• rs148214051
• NM_005847.5:c.1051C>G

Variant summary

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

The NM_005847.5(SLC23A1):​c.1051C>G​(p.Pro351Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.99

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A1	NM_005847.5	c.1051C>G	p.Pro351Ala	missense_variant	Exon 9 of 15	ENST00000348729.8	NP_005838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8	c.1051C>G	p.Pro351Ala	missense_variant	Exon 9 of 15	1	NM_005847.5	ENSP00000302701.4
SLC23A1	ENST00000353963.7	c.1063C>G	p.Pro355Ala	missense_variant	Exon 9 of 15	1		ENSP00000302851.5
SLC23A1	ENST00000504513.1	c.289C>G	p.Pro97Ala	missense_variant	Exon 3 of 4	5		ENSP00000422688.1
SLC23A1	ENST00000506512.1	n.*102C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251394 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.69	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.7	D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0090	D;D
Vest4		0.61
MutPred		0.51		.;Loss of glycosylation at P351 (P = 0.0059);
MVP		0.77
MPC		1.6
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.87

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: rs148214051; hg19: chr5-138714918;