NM_021082.4:c.220T>A

Variant names:

• chr3-121897414-T-A
• rs752943810
• NM_021082.4:c.220T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021082.4(SLC15A2):​c.220T>A​(p.Phe74Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC15A2 NM_021082.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34791565).

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.220T>A	p.Phe74Ile	missense	Exon 3 of 22	NP_066568.3
	SLC15A2	NM_001145998.2		c.220T>A	p.Phe74Ile	missense	Exon 3 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.220T>A	p.Phe74Ile	missense	Exon 3 of 22	ENSP00000417085.1	Q16348-1
	SLC15A2	ENST00000966832.1		c.220T>A	p.Phe74Ile	missense	Exon 3 of 22	ENSP00000636891.1
	SLC15A2	ENST00000886960.1		c.220T>A	p.Phe74Ile	missense	Exon 3 of 22	ENSP00000557019.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	0.049
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
PhyloP100		7.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.013	D
Sift4G	Benign	0.095	T
Polyphen		0.0080	B
Vest4		0.49
MutPred		0.36		Loss of helix (P = 0.1706)
MVP		0.52
MPC		0.11
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.55
gMVP		0.70
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs752943810; hg19: chr3-121616261;