rs1143671

chr3-121928439-C-Achr3-121928439-C-Gchr3-121928439-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021082.4(SLC15A2):c.1225C>A(p.Pro409Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P409S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC15A2 NM_021082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

SLC15A2 (HGNC:10921): (solute carrier family 15 member 2) The mammalian kidney expresses a proton-coupled peptide transporter that is responsible for the absorption of small peptides, as well as beta-lactam antibiotics and other peptide-like drugs, from the tubular filtrate. This transporter, SLC15A2, belongs to the same gene family as SLC15A1 (MIM 600544), the proton-coupled peptide transporter found in the small intestine (Liu et al, 1995 [PubMed 7756356]).[supplied by OMIM, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20779133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A2	NM_021082.4	c.1225C>A	p.Pro409Thr	missense_variant	15/22	ENST00000489711.6
SLC15A2	NM_001145998.2	c.1132C>A	p.Pro378Thr	missense_variant	14/21
SLC15A2	XM_005247722.4	c.1225C>A	p.Pro409Thr	missense_variant	15/21
SLC15A2	XM_006713736.4	c.1225C>A	p.Pro409Thr	missense_variant	15/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1225C>A	p.Pro409Thr	missense_variant	15/22	1	NM_021082.4	P1
SLC15A2	ENST00000295605.6	c.1132C>A	p.Pro378Thr	missense_variant	14/21	2
SLC15A2	ENST00000465060.1	n.148C>A		non_coding_transcript_exon_variant	1/4	3
SLC15A2	ENST00000489957.1	n.200C>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	16
Dann	Benign	0.97
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Benign	0.048
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.050	T;D
Polyphen		0.99	D;.
Vest4		0.060
MutPred		0.44		Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.39
MPC		0.15
ClinPred		0.89	D
GERP RS		-0.53
Varity_R		0.33
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1143671; hg19: chr3-121647286;