5-139382020-G-C

Variant names:

• chr5-139382020-G-C
• rs6886922
• NM_005847.5:c.180C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152685.4(SLC23A1):​c.180C>G​(p.Ile60Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC23A1 NM_152685.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152685.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A1	NM_005847.5	MANE Select	c.180C>G	p.Ile60Met	missense	Exon 3 of 15	NP_005838.3
	SLC23A1	NM_152685.4		c.180C>G	p.Ile60Met	missense	Exon 3 of 15	NP_689898.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A1	ENST00000348729.8	TSL:1 MANE Select	c.180C>G	p.Ile60Met	missense	Exon 3 of 15	ENSP00000302701.4
	SLC23A1	ENST00000353963.7	TSL:1	c.180C>G	p.Ile60Met	missense	Exon 3 of 15	ENSP00000302851.5
	SLC23A1	ENST00000882127.1		c.180C>G	p.Ile60Met	missense	Exon 4 of 16	ENSP00000552186.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456766 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724044

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 43992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 85108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109746

Other (OTH) AF: 0.00 AC: 0 AN: 60184

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	0.10
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.79	T
PhyloP100		-0.51
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Benign	0.097	T
Sift4G	Benign	0.10	T
Vest4		0.59
MutPred		0.82		Loss of glycosylation at S57 (P = 0.0732)
MVP		0.53
MPC		0.14
ClinPred		0.79	D
GERP RS		0.52
gMVP		0.75
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs6886922; hg19: chr5-138717709;