chr12-84870610-C-A

Variant names:

• chr12-84870610-C-A
• rs146564303
• NM_182767.6:c.1363G>T

Variant summary

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

The NM_182767.6(SLC6A15):​c.1363G>T​(p.Ala455Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A455T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A15 NM_182767.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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

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 rank	MANE	Protein	UniProt
SLC6A15	NM_182767.6	c.1363G>T	p.Ala455Ser	missense_variant	Exon 9 of 12	ENST00000266682.10	NP_877499.1
SLC6A15	NM_001146335.3	c.1042G>T	p.Ala348Ser	missense_variant	Exon 8 of 11		NP_001139807.1
SLC6A15	XM_011538525.4	c.1363G>T	p.Ala455Ser	missense_variant	Exon 9 of 10		XP_011536827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A15	ENST00000266682.10	c.1363G>T	p.Ala455Ser	missense_variant	Exon 9 of 12	1	NM_182767.6	ENSP00000266682.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.066	T;T;T
Polyphen		0.93	P;P;.
Vest4		0.57
MutPred		0.63		Gain of catalytic residue at W459 (P = 5e-04);.;.;
MVP		0.84
MPC		0.51
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.44
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146564303; hg19: chr12-85264389;