12-84863542-A-G

Variant names:

• chr12-84863542-A-G
• NM_182767.6:c.1715T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182767.6(SLC6A15):​c.1715T>C​(p.Met572Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A15 NM_182767.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22
• Publications: 0 publications found

Genes affected

SLC6A15 (HGNC:13621): (solute carrier family 6 member 15) This gene encodes a member of the solute carrier family 6 protein family which transports neutral amino acids. The encoded protein is thought to play a role in neuronal amino acid transport (PMID: 16185194) and may be associated with major depression (PMID: 21521612). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2997348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182767.6. 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
	SLC6A15	NM_182767.6	MANE Select	c.1715T>C	p.Met572Thr	missense	Exon 11 of 12	NP_877499.1	Q9H2J7-1
	SLC6A15	NM_001146335.3		c.1394T>C	p.Met465Thr	missense	Exon 10 of 11	NP_001139807.1	Q9H2J7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A15	ENST00000266682.10	TSL:1 MANE Select	c.1715T>C	p.Met572Thr	missense	Exon 11 of 12	ENSP00000266682.5	Q9H2J7-1
	SLC6A15	ENST00000680963.1		c.1715T>C	p.Met572Thr	missense	Exon 11 of 12	ENSP00000505485.1	Q9H2J7-1
	SLC6A15	ENST00000681106.1		c.1715T>C	p.Met572Thr	missense	Exon 12 of 13	ENSP00000505789.1	Q9H2J7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	0.0083	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.61
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.38	N
PhyloP100		4.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	0.99	T
Polyphen		0.0	B
Vest4		0.50
MutPred		0.63		Gain of catalytic residue at R567 (P = 2e-04)
MVP		0.70
MPC		0.35
ClinPred		0.75	D
GERP RS		5.7
Varity_R		0.19
gMVP		0.81
Mutation Taster		=63/37	polymorphism

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

hg19: chr12-85257321;