Genetic Variant SLC15A1:p.Ser117Asn (chr13-98723927-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005073.4(SLC15A1):c.350G>A(p.Ser117Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,613,912 control chromosomes in the GnomAD database, including 24,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3920 hom., cov: 32)

Exomes 𝑓: 0.14 ( 20186 hom. )

Consequence

SLC15A1
NM_005073.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

42 publications found

Variant links:

Genes affected

SLC15A1 (HGNC:10920): (solute carrier family 15 member 1) This gene encodes an intestinal hydrogen peptide cotransporter that is a member of the solute carrier family 15. The encoded protein is localized to the brush border membrane of the intestinal epithelium and mediates the uptake of di- and tripeptides from the lumen into the enterocytes. This protein plays an important role in the uptake and digestion of dietary proteins. This protein also facilitates the absorption of numerous peptidomimetic drugs. [provided by RefSeq, Apr 2010]

SLC15A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.016327E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A1	NM_005073.4 link	c.350G>A	p.Ser117Asn	missense_variant	Exon 5 of 23	ENST00000376503.10	NP_005064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A1	ENST00000376503.10 link	c.350G>A	p.Ser117Asn	missense_variant	Exon 5 of 23	1	NM_005073.4	ENSP00000365686.4
SLC15A1	ENST00000376494.1 link	n.447G>A		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30794

AN:

152032

Hom.:

3921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.217

AC:

54618

AN:

251326

AF XY:

0.212

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.328

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.441

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.140

AC:

204600

AN:

1461762

Hom.:

20186

Cov.:

AF XY:

0.144

AC XY:

104851

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.315

AC:

10534

AN:

33470

American (AMR)

AF:

0.313

AC:

13978

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4581

AN:

26134

East Asian (EAS)

AF:

0.424

AC:

16846

AN:

39694

South Asian (SAS)

AF:

0.305

AC:

26314

AN:

86250

European-Finnish (FIN)

AF:

0.210

AC:

11221

AN:

53406

Middle Eastern (MID)

AF:

0.211

AC:

1217

AN:

5760

European-Non Finnish (NFE)

AF:

0.0988

AC:

109815

AN:

1111942

Other (OTH)

AF:

0.167

AC:

10094

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8318

16635

24953

33270

41588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4446

8892

13338

17784

22230

<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:

0.203

AC:

30813

AN:

152150

Hom.:

3920

Cov.:

AF XY:

0.212

AC XY:

15787

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.305

AC:

12653

AN:

41506

American (AMR)

AF:

0.227

AC:

3468

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

591

AN:

3468

East Asian (EAS)

AF:

0.435

AC:

2248

AN:

5172

South Asian (SAS)

AF:

0.319

AC:

1535

AN:

4810

European-Finnish (FIN)

AF:

0.242

AC:

2563

AN:

10578

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7140

AN:

68016

Other (OTH)

AF:

0.202

AC:

424

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1143

2287

3430

4574

5717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.139

Hom.:

8735

Bravo

AF:

0.211

TwinsUK

AF:

0.0955

AC:

354

ALSPAC

AF:

0.113

AC:

437

ESP6500AA

AF:

0.298

AC:

1315

ESP6500EA

AF:

0.110

AC:

947

ExAC

AF:

0.214

AC:

25953

Asia WGS

AF:

0.378

AC:

1311

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0050

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.041

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.77

MetaRNN

Benign

0.00050

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.55

PhyloP100

-1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

2.2

REVEL

Benign

0.092

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.042

MPC

0.044

ClinPred

0.011

GERP RS

-11

Varity_R

0.032

gMVP

0.57

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

Other links and lift over