chr12-84861813-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182767.6(SLC6A15):​c.2012G>A​(p.Gly671Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SLC6A15
NM_182767.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07743028).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A15NM_182767.6 linkc.2012G>A p.Gly671Asp missense_variant Exon 12 of 12 ENST00000266682.10 NP_877499.1 Q9H2J7-1
SLC6A15NM_001146335.3 linkc.1691G>A p.Gly564Asp missense_variant Exon 11 of 11 NP_001139807.1 Q9H2J7-3Q9NW50Q8IXG2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A15ENST00000266682.10 linkc.2012G>A p.Gly671Asp missense_variant Exon 12 of 12 1 NM_182767.6 ENSP00000266682.5 Q9H2J7-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152044
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251194
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
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:
0.000163
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461754
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
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:
0.0000497
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152044
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2012G>A (p.G671D) alteration is located in exon 12 (coding exon 11) of the SLC6A15 gene. This alteration results from a G to A substitution at nucleotide position 2012, causing the glycine (G) at amino acid position 671 to be replaced by an aspartic acid (D). 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
0.091
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
19
DANN
Benign
0.80
DEOGEN2
Benign
0.030
T;.
Eigen
Benign
-0.075
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.077
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.46
N;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
1.1
N;N
REVEL
Benign
0.16
Sift
Benign
0.54
T;T
Sift4G
Benign
0.83
T;T
Polyphen
0.0010
B;.
Vest4
0.19
MutPred
0.32
Gain of catalytic residue at L676 (P = 0.0747);.;
MVP
0.70
MPC
0.40
ClinPred
0.31
T
GERP RS
5.8
Varity_R
0.14
gMVP
0.61

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

LitVar

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

Other links and lift over

dbSNP: rs773511911; hg19: chr12-85255592; API