chr5-139378320-G-C

Variant names:

• chr5-139378320-G-C
• rs774710051
• NM_005847.5:c.1211C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005847.5(SLC23A1):​c.1211C>G​(p.Ala404Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A404V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005847.5. 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
	SLC23A1	NM_005847.5	MANE Select	c.1211C>G	p.Ala404Gly	missense	Exon 11 of 15	NP_005838.3
	SLC23A1	NM_152685.4		c.1223C>G	p.Ala408Gly	missense	Exon 11 of 15	NP_689898.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A1	ENST00000348729.8	TSL:1 MANE Select	c.1211C>G	p.Ala404Gly	missense	Exon 11 of 15	ENSP00000302701.4	Q9UHI7-1
	SLC23A1	ENST00000353963.7	TSL:1	c.1223C>G	p.Ala408Gly	missense	Exon 11 of 15	ENSP00000302851.5	Q9UHI7-2
	SLC23A1	ENST00000882127.1		c.1211C>G	p.Ala404Gly	missense	Exon 12 of 16	ENSP00000552186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.86	T
PhyloP100		8.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.23
Sift	Benign	0.58	T
Sift4G	Benign	0.57	T
Vest4		0.53
MutPred		0.72		Loss of sheet (P = 0.0817)
MVP		0.55
MPC		1.0
ClinPred		0.95	D
GERP RS		5.3
gMVP		0.87
Mutation Taster		=15/85	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs774710051; hg19: chr5-138714009;