12-16244743-G-T

Position:

• chr12-16244743-G-T

Variant summary

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

The NM_001170798.1(SLC15A5):​c.812C>A​(p.Pro271Gln) 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. 15/19 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. P271L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC15A5 NM_001170798.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71

Genes affected

SLC15A5 (HGNC:33455): (solute carrier family 15 member 5) Predicted to enable symporter activity. Predicted to be involved in peptide transport; protein transport; and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC101928362 (HGNC:):

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=0.10030934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A5	NM_001170798.1	c.812C>A	p.Pro271Gln	missense_variant	4/9	ENST00000344941.3	NP_001164269.1
LOC101928362	XR_001749028.1	n.334-88G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A5	ENST00000344941.3	c.812C>A	p.Pro271Gln	missense_variant	4/9	5	NM_001170798.1	ENSP00000340402	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.17
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.060
Sift	Benign	0.38	T
Sift4G	Uncertain	0.057	T
Vest4		0.17
MutPred		0.46		Gain of catalytic residue at K267 (P = 0);
MVP		0.030
ClinPred		0.076	T
GERP RS		2.4
Varity_R		0.027
gMVP		0.25

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: rs1527014; hg19: chr12-16397677;