13-98687583-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005073.4(SLC15A1):c.1825C>G(p.Gln609Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC15A1 NM_005073.4 missense, splice_region
• Scores: Splicing: ADA: 0.9212
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A1	NM_005073.4	c.1825C>G	p.Gln609Glu	missense_variant, splice_region_variant	21/23	ENST00000376503.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A1	ENST00000376503.10	c.1825C>G	p.Gln609Glu	missense_variant, splice_region_variant	21/23	1	NM_005073.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 15, 2023

The c.1825C>G (p.Q609E) alteration is located in exon 21 (coding exon 21) of the SLC15A1 gene. This alteration results from a C to G substitution at nucleotide position 1825, causing the glutamine (Q) at amino acid position 609 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
Cadd	Pathogenic	28
Dann	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Benign	0.050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.33		Gain of disorder (P = 0.0707);
MVP		0.45
MPC		0.28
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.56
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-99339837;