3-121928439-C-G

Variant names:

• chr3-121928439-C-G
• rs1143671
• NM_021082.4:c.1225C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021082.4(SLC15A2):​c.1225C>G​(p.Pro409Ala) 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. 14/22 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: SLC15A2 NM_021082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 69 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16087651).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021082.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A2	NM_021082.4	MANE Select	c.1225C>G	p.Pro409Ala	missense	Exon 15 of 22	NP_066568.3
	SLC15A2	NM_001145998.2		c.1132C>G	p.Pro378Ala	missense	Exon 14 of 21	NP_001139470.1	Q16348-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A2	ENST00000489711.6	TSL:1 MANE Select	c.1225C>G	p.Pro409Ala	missense	Exon 15 of 22	ENSP00000417085.1	Q16348-1
	SLC15A2	ENST00000966832.1		c.1237C>G	p.Pro413Ala	missense	Exon 15 of 22	ENSP00000636891.1
	SLC15A2	ENST00000886960.1		c.1222C>G	p.Pro408Ala	missense	Exon 15 of 22	ENSP00000557019.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 60233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.82
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.073
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.046
Sift	Benign	0.034	D
Sift4G	Uncertain	0.023	D
Polyphen		0.66	P
Vest4		0.091
MutPred		0.50		Loss of sheet (P = 0.0181)
MVP		0.29
MPC		0.11
ClinPred		0.64	D
GERP RS		-0.53
Varity_R		0.12
gMVP		0.49
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1143671; hg19: chr3-121647286;