chr5-139378327-A-G

Variant names:

• chr5-139378327-A-G
• rs1389684301
• NM_005847.5:c.1204T>C

Variant summary

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

The NM_005847.5(SLC23A1):​c.1204T>C​(p.Tyr402His) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,425,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y402D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SLC23A1 NM_005847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11
• Publications: 0 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.1204T>C	p.Tyr402His	missense	Exon 11 of 15	NP_005838.3
	SLC23A1	NM_152685.4		c.1216T>C	p.Tyr406His	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.1204T>C	p.Tyr402His	missense	Exon 11 of 15	ENSP00000302701.4	Q9UHI7-1
	SLC23A1	ENST00000353963.7	TSL:1	c.1216T>C	p.Tyr406His	missense	Exon 11 of 15	ENSP00000302851.5	Q9UHI7-2
	SLC23A1	ENST00000882127.1		c.1204T>C	p.Tyr402His	missense	Exon 12 of 16	ENSP00000552186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000532 AC: 1 AN: 188108 AF XY: 0.00000987

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425210 Hom.: 0 Cov.: 33 AF XY: 0.00000142 AC XY: 1 AN XY: 705644

African (AFR) AF: 0.00 AC: 0 AN: 32592

American (AMR) AF: 0.00 AC: 0 AN: 39180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 37578

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094592

Other (OTH) AF: 0.00 AC: 0 AN: 58958

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
PhyloP100		6.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Benign	0.38	T
Sift4G	Benign	0.48	T
Vest4		0.71
MutPred		0.65		Loss of sheet (P = 0.0817)
MVP		0.54
MPC		1.8
ClinPred		0.95	D
GERP RS		5.3
gMVP		0.79
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1389684301; hg19: chr5-138714016;