rs3765108

Variant names:

• chr12-128793662-T-C
• rs3765108
• NM_145648.4:c.*534A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145648.4(SLC15A4):​c.*534A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,082 control chromosomes in the GnomAD database, including 6,155 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 0.27 (6154 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: SLC15A4 NM_145648.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	NM_145648.4	MANE Select	c.*534A>G		3_prime_UTR	Exon 8 of 8	NP_663623.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A4	ENST00000266771.10	TSL:1 MANE Select	c.*534A>G		3_prime_UTR	Exon 8 of 8	ENSP00000266771.5
	SLC15A4	ENST00000376744.8	TSL:2	n.*1220A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000365935.4
	SLC15A4	ENST00000376744.8	TSL:2	n.*1220A>G		3_prime_UTR	Exon 7 of 7	ENSP00000365935.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41487 AN: 151942 Hom.: 6142 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.188 AC: 3 AN: 16

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.273 AC: 41516 AN: 152060 Hom.: 6154 Cov.: 32 AF XY: 0.274 AC XY: 20330 AN XY: 74328

African (AFR) AF: 0.162 AC: 6720 AN: 41498

American (AMR) AF: 0.280 AC: 4281 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1004 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1655 AN: 5172

South Asian (SAS) AF: 0.169 AC: 817 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 3981 AN: 10534

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22257 AN: 67968

Other (OTH) AF: 0.268 AC: 565 AN: 2110

Alfa AF: 0.300 Hom.: 4285

Bravo AF: 0.263

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.075
DANN	Benign	0.61
PhyloP100		-1.0
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: rs3765108; hg19: chr12-129278207;