dbSNP rs35817838: SLC23A1:p.Met258Val (chr5-139379831-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005847.5(SLC23A1):c.772A>G(p.Met258Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,613,970 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 108 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 94 hom. )

Consequence

SLC23A1
NM_005847.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71

Publications

15 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048335493).

BP6

Variant 5-139379831-T-C is Benign according to our data. Variant chr5-139379831-T-C is described in ClinVar as Benign. ClinVar VariationId is 785139.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A1	NM_005847.5 link	c.772A>G	p.Met258Val	missense_variant	Exon 8 of 15	ENST00000348729.8	NP_005838.3	Q9UHI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC23A1	ENST00000348729.8 link	c.772A>G	p.Met258Val	missense_variant	Exon 8 of 15	1	NM_005847.5	ENSP00000302701.4	Q9UHI7-1
SLC23A1	ENST00000353963.7 link	c.784A>G	p.Met262Val	missense_variant	Exon 8 of 15	1		ENSP00000302851.5	Q9UHI7-2
SLC23A1	ENST00000506512.1 link	n.383A>G		non_coding_transcript_exon_variant	Exon 1 of 2	4
SLC23A1	ENST00000504513.1 link	c.163+125A>G		intron_variant	Intron 2 of 3	5		ENSP00000422688.1	H0Y902

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2943

AN:

151978

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0681

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00506

AC:

1271

AN:

251322

AF XY:

0.00374

show subpopulations

Gnomad AFR exome

AF:

0.0695

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00200

AC:

2922

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1247

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0691

AC:

2312

AN:

33478

American (AMR)

AF:

0.00329

AC:

147

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000842

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000220

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000112

AC:

124

AN:

1112004

Other (OTH)

AF:

0.00445

AC:

269

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

176

352

527

703

879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0195

AC:

2971

AN:

152096

Hom.:

108

Cov.:

AF XY:

0.0184

AC XY:

1369

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0685

AC:

2843

AN:

41480

American (AMR)

AF:

0.00563

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00104

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67978

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00748

Hom.:

Bravo

AF:

0.0217

ESP6500AA

AF:

0.0708

AC:

312

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00621

AC:

754

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.5

(source)

DANN

Benign

0.39

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.38

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.99

PhyloP100

2.7

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.77

N;N

REVEL

Benign

0.12

Sift

Benign

0.23

T;T

Sift4G

Benign

0.13

T;T

Vest4

0.14

MVP

0.17

MPC

0.78

ClinPred

0.0049

GERP RS

0.68

gMVP

0.57

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over