13-98706192-T-G

Position:

• chr13-98706192-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_005073.4(SLC15A1):​c.1211A>C​(p.Asn404Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)
• Consequence: SLC15A1 NM_005073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.405

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity S15A1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1429362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A1	NM_005073.4	c.1211A>C	p.Asn404Thr	missense_variant	16/23	ENST00000376503.10	NP_005064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A1	ENST00000376503.10	c.1211A>C	p.Asn404Thr	missense_variant	16/23	1	NM_005073.4	ENSP00000365686.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.1211A>C (p.N404T) alteration is located in exon 16 (coding exon 16) of the SLC15A1 gene. This alteration results from a A to C substitution at nucleotide position 1211, causing the asparagine (N) at amino acid position 404 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.7
DANN	Benign	0.93
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.056
Sift	Benign	0.081	T
Sift4G	Benign	0.18	T
Polyphen		0.031	B
Vest4		0.20
MutPred		0.68		Loss of loop (P = 0.0374);
MVP		0.030
MPC		0.049
ClinPred		0.26	T
GERP RS		-0.32
Varity_R		0.17
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs1001738851; hg19: chr13-99358446;