11-60937917-G-A

Position:

• chr11-60937917-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016582.3(SLC15A3):​c.1544C>T​(p.Ala515Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC15A3 NM_016582.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

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]

SLC15A3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A3	NM_016582.3	c.1544C>T	p.Ala515Val	missense_variant	7/8	ENST00000227880.8	NP_057666.1
SLC15A3	XM_011545095.3	c.1544C>T	p.Ala515Val	missense_variant	7/9		XP_011543397.1
SLC15A3	NR_027391.2	n.2000C>T		non_coding_transcript_exon_variant	6/7
SLC15A3	XR_007062485.1	n.2000C>T		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A3	ENST00000227880.8	c.1544C>T	p.Ala515Val	missense_variant	7/8	1	NM_016582.3	ENSP00000227880.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.1544C>T (p.A515V) alteration is located in exon 7 (coding exon 7) of the SLC15A3 gene. This alteration results from a C to T substitution at nucleotide position 1544, causing the alanine (A) at amino acid position 515 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0081	.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;D
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.0	D;N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.66	.;P
Vest4		0.42
MutPred		0.48		.;Gain of sheet (P = 0.1945);
MVP		0.83
MPC		0.23
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-60705389;