chr13-98723927-C-T

Position:

• chr13-98723927-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S117R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.20 (3920 hom., cov: 32)
  • Exomes 𝑓: 0.14 (20186 hom.)
• Consequence: SLC15A1 NM_005073.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC15A1	NM_005073.4	c.350G>A	p.Ser117Asn	missense_variant	5/23	ENST00000376503.10	NP_005064.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30794 AN: 152032 Hom.: 3921 Cov.: 32

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

GnomAD3 exomes AF: 0.217 AC: 54618 AN: 251326 Hom.: 7716 AF XY: 0.212 AC XY: 28817 AN XY: 135840

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 SAS exome AF: 0.313

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.: 32 AF XY: 0.144 AC XY: 104851 AN XY: 727182

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.0988

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.203 AC: 30813 AN: 152150 Hom.: 3920 Cov.: 32 AF XY: 0.212 AC XY: 15787 AN XY: 74384

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.202

Alfa AF: 0.135 Hom.: 4548

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	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0050
DANN	Benign	0.78
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.00050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.092
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.044
ClinPred		0.011	T
GERP RS		-11
Varity_R		0.032
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs2297322; hg19: chr13-99376181; COSMIC: COSV64711910;