chr12-84870610-C-T

Variant summary

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

The NM_182767.6(SLC6A15):​c.1363G>A​(p.Ala455Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC6A15
NM_182767.6 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77
Variant links:
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]

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ACMG classification

Classification made for transcript

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
SLC6A15NM_182767.6 linkc.1363G>A p.Ala455Thr missense_variant Exon 9 of 12 ENST00000266682.10 NP_877499.1 Q9H2J7-1
SLC6A15NM_001146335.3 linkc.1042G>A p.Ala348Thr missense_variant Exon 8 of 11 NP_001139807.1 Q9H2J7-3Q9NW50Q8IXG2
SLC6A15XM_011538525.4 linkc.1363G>A p.Ala455Thr missense_variant Exon 9 of 10 XP_011536827.1 A0A7P0T8I1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A15ENST00000266682.10 linkc.1363G>A p.Ala455Thr missense_variant Exon 9 of 12 1 NM_182767.6 ENSP00000266682.5 Q9H2J7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249536
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134870
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459770
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1363G>A (p.A455T) alteration is located in exon 9 (coding exon 8) of the SLC6A15 gene. This alteration results from a G to A substitution at nucleotide position 1363, causing the alanine (A) at amino acid position 455 to be replaced by a threonine (T). 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
0.14
BayesDel_addAF
Benign
-0.037
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.35
T;T;.
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.061
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Uncertain
0.11
D
MutationAssessor
Pathogenic
3.4
M;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Uncertain
0.48
Sift
Uncertain
0.0060
D;D;D
Sift4G
Benign
0.067
T;T;T
Polyphen
0.98
D;D;.
Vest4
0.70
MVP
0.90
MPC
0.71
ClinPred
0.74
D
GERP RS
5.6
Varity_R
0.58
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146564303; hg19: chr12-85264389; API