Genetic Variant NM_005847.5:c.180C>G (chr5-139382020-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005847.5(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_005847.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.511

Variant links:

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]

SLC23A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A1	NM_005847.5 link	c.180C>G	p.Ile60Met	missense_variant	Exon 3 of 15	ENST00000348729.8	NP_005838.3	Q9UHI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8 link	c.180C>G	p.Ile60Met	missense_variant	Exon 3 of 15	1	NM_005847.5	ENSP00000302701.4		Q9UHI7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724044

show subpopulations

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.10

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.93

.;.;D

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.79

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;N;D

REVEL

Benign

0.24

Sift

Benign

0.097

T;T;D

Sift4G

Benign

0.10

T;T;.

Vest4

0.59

MutPred

0.82

Loss of glycosylation at S57 (P = 0.0732);Loss of glycosylation at S57 (P = 0.0732);.;

MVP

0.53

MPC

0.14

ClinPred

0.79

GERP RS

0.52

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over