rs10847697

Variant names:

• chr12-128814840-G-A
• rs10847697
• NM_145648.4:c.777C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145648.4(SLC15A4):​c.777C>T​(p.Asp259Asp) 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
• Publications: 39 publications found

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]

ENSG00000279500 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145648.4. 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
	SLC15A4	NM_145648.4	MANE Select	c.777C>T	p.Asp259Asp	synonymous	Exon 2 of 8	NP_663623.1	Q8N697-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	ENST00000266771.10	TSL:1 MANE Select	c.777C>T	p.Asp259Asp	synonymous	Exon 2 of 8	ENSP00000266771.5	Q8N697-1
	SLC15A4	ENST00000923390.1		c.927C>T	p.Asp309Asp	synonymous	Exon 2 of 8	ENSP00000593449.1
	SLC15A4	ENST00000964262.1		c.777C>T	p.Asp259Asp	synonymous	Exon 2 of 8	ENSP00000634321.1

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

GnomAD2 exomes AF: 0.131 AC: 32970 AN: 251396 AF XY: 0.132

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 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

African (AFR) AF: 0.0170 AC: 570 AN: 33478

American (AMR) AF: 0.239 AC: 10687 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 2374 AN: 26132

East Asian (EAS) AF: 0.176 AC: 6988 AN: 39698

South Asian (SAS) AF: 0.181 AC: 15628 AN: 86250

European-Finnish (FIN) AF: 0.104 AC: 5551 AN: 53416

Middle Eastern (MID) AF: 0.138 AC: 797 AN: 5766

European-Non Finnish (NFE) AF: 0.106 AC: 118275 AN: 1111908

Other (OTH) AF: 0.114 AC: 6884 AN: 60394

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

African (AFR) AF: 0.0214 AC: 889 AN: 41560

American (AMR) AF: 0.197 AC: 3015 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3468

East Asian (EAS) AF: 0.184 AC: 953 AN: 5186

South Asian (SAS) AF: 0.174 AC: 837 AN: 4814

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10598

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6860 AN: 68016

Other (OTH) AF: 0.117 AC: 246 AN: 2110

Alfa AF: 0.105 Hom.: 2038

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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