11-60948240-C-T

Variant names:

• chr11-60948240-C-T
• rs566353
• NM_016582.3:c.559-1419G>A

Variant summary

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

The NM_016582.3(SLC15A3):​c.559-1419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,034 control chromosomes in the GnomAD database, including 11,668 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 0.37 (11668 hom., cov: 32)
• Consequence: SLC15A3 NM_016582.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 12 publications found

Genes affected

SLC15A3 (HGNC:18068): (solute carrier family 15 member 3) Enables dipeptide transmembrane transporter activity. Involved in dipeptide import across plasma membrane. Located in intracellular membrane-bounded organelle. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A3	NM_016582.3	c.559-1419G>A		intron_variant	Intron 1 of 7	ENST00000227880.8	NP_057666.1
SLC15A3	NR_027391.2	n.1184-1419G>A		intron_variant	Intron 1 of 6
SLC15A3	XM_011545095.3	c.559-1419G>A		intron_variant	Intron 1 of 8		XP_011543397.1
SLC15A3	XR_007062485.1	n.1184-1419G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A3	ENST00000227880.8	c.559-1419G>A		intron_variant	Intron 1 of 7	1	NM_016582.3	ENSP00000227880.2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55582 AN: 151918 Hom.: 11666 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.366 AC: 55617 AN: 152034 Hom.: 11668 Cov.: 32 AF XY: 0.365 AC XY: 27119 AN XY: 74336

African (AFR) AF: 0.159 AC: 6579 AN: 41464

American (AMR) AF: 0.433 AC: 6607 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1522 AN: 5172

South Asian (SAS) AF: 0.425 AC: 2048 AN: 4820

European-Finnish (FIN) AF: 0.397 AC: 4182 AN: 10546

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31567 AN: 67978

Other (OTH) AF: 0.396 AC: 835 AN: 2106

Alfa AF: 0.443 Hom.: 25807

Bravo AF: 0.357

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.036
DANN	Benign	0.75
PhyloP100		-2.2
PromoterAI		-0.0092	Neutral
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: rs566353; hg19: chr11-60715712;