chr13-98723927-C-T

Variant names:

• chr13-98723927-C-T
• rs2297322
• NM_005073.4:c.350G>A

Variant summary

Our verdict is Benign. The variant received -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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 42 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005073.4. 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
	SLC15A1	NM_005073.4	MANE Select	c.350G>A	p.Ser117Asn	missense	Exon 5 of 23	NP_005064.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A1	ENST00000376503.10	TSL:1 MANE Select	c.350G>A	p.Ser117Asn	missense	Exon 5 of 23	ENSP00000365686.4
	SLC15A1	ENST00000376494.1	TSL:5	n.447G>A		non_coding_transcript_exon	Exon 3 of 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

GnomAD2 exomes AF: 0.217 AC: 54618 AN: 251326 AF XY: 0.212

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

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

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

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: 72 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7140 AN: 68016

Other (OTH) AF: 0.202 AC: 424 AN: 2102

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 v4.9

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
PhyloP100		-1.1
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
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

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