rs1527014

Positions:

• chr12-16244743-G-A
• chr12-16244743-G-C
• chr12-16244743-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170798.1(SLC15A5):​c.812C>T​(p.Pro271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,537,704 control chromosomes in the GnomAD database, including 710,541 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.94 (67612 hom., cov: 33)
  • Exomes 𝑓: 0.96 (642929 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3576243E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A5	NM_001170798.1	c.812C>T	p.Pro271Leu	missense_variant	4/9	ENST00000344941.3	NP_001164269.1
LOC101928362	XR_001749028.1	n.334-88G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A5	ENST00000344941.3	c.812C>T	p.Pro271Leu	missense_variant	4/9	5	NM_001170798.1	ENSP00000340402	P1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143275 AN: 152188 Hom.: 67559 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.956

GnomAD3 exomes AF: 0.959 AC: 137981 AN: 143936 Hom.: 66191 AF XY: 0.963 AC XY: 73760 AN XY: 76606

Gnomad AFR exome AF: 0.869

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 0.994

Gnomad SAS exome AF: 0.977

Gnomad FIN exome AF: 0.940

Gnomad NFE exome AF: 0.966

Gnomad OTH exome AF: 0.968

GnomAD4 exome AF: 0.963 AC: 1334468 AN: 1385398 Hom.: 642929 Cov.: 68 AF XY: 0.964 AC XY: 659183 AN XY: 683594

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.981

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.979

Gnomad4 FIN exome AF: 0.943

Gnomad4 NFE exome AF: 0.965

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.941 AC: 143383 AN: 152306 Hom.: 67612 Cov.: 33 AF XY: 0.941 AC XY: 70108 AN XY: 74476

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.956

Alfa AF: 0.963 Hom.: 128769

Bravo AF: 0.938

TwinsUK AF: 0.969 AC: 3594

ALSPAC AF: 0.969 AC: 3733

ESP6500AA AF: 0.880 AC: 1218

ESP6500EA AF: 0.966 AC: 3074

ExAC AF: 0.956 AC: 21681

Asia WGS AF: 0.980 AC: 3408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.29
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.070
Sift	Benign	0.54	T
Sift4G	Benign	1.0	T
Vest4		0.049
ClinPred		0.0080	T
GERP RS		2.4
Varity_R		0.025
gMVP		0.19

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;