rs10847697

chr12-128814840-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145648.4(SLC15A4):c.777C>T(p.Asp259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,998 control chromosomes in the GnomAD database, including 11,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (931 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10806 hom.)
• Consequence: SLC15A4 NM_145648.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

Genes affected

SLC15A4 (HGNC:23090): (solute carrier family 15 member 4) Enables L-histidine transmembrane transporter activity; peptide transmembrane transporter activity; and peptidoglycan transmembrane transporter activity. Involved in several processes, including dipeptide import across plasma membrane; peptidoglycan transport; and positive regulation of toll-like receptor signaling pathway. Located in endolysosome membrane. Is integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.545 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A4	NM_145648.4	c.777C>T	p.Asp259=	synonymous_variant	2/8	ENST00000266771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A4	ENST00000266771.10	c.777C>T	p.Asp259=	synonymous_variant	2/8	1	NM_145648.4	P1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14393 AN: 152114 Hom.: 921 Cov.: 33

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.131 AC: 32970 AN: 251396 Hom.: 2664 AF XY: 0.132 AC XY: 17927 AN XY: 135886

Gnomad AFR exome AF: 0.0194

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.0858

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.115 AC: 167754 AN: 1461764 Hom.: 10806 Cov.: 32 AF XY: 0.116 AC XY: 84631 AN XY: 727170

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0946 AC: 14406 AN: 152234 Hom.: 931 Cov.: 33 AF XY: 0.101 AC XY: 7498 AN XY: 74424

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0943

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.117

Alfa AF: 0.106 Hom.: 1662

Bravo AF: 0.0972

Asia WGS AF: 0.154 AC: 534 AN: 3478

EpiCase AF: 0.101

EpiControl AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.32

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: rs10847697; hg19: chr12-129299385; COSMIC: COSV57160420; COSMIC: COSV57160420;