Genetic Variant NM_182767.6:c.2186A>T (chr12-84861639-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182767.6(SLC6A15):c.2186A>T(p.Asp729Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,590,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC6A15
NM_182767.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

Publications

0 publications found

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]

SLC6A15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19511732).

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.2186A>T	p.Asp729Val	missense	Exon 12 of 12	NP_877499.1	Q9H2J7-1
	SLC6A15	NM_001146335.3		c.1865A>T	p.Asp622Val	missense	Exon 11 of 11	NP_001139807.1	Q9H2J7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC6A15	ENST00000266682.10	TSL:1 MANE Select	c.2186A>T	p.Asp729Val	missense	Exon 12 of 12	ENSP00000266682.5	Q9H2J7-1
SLC6A15	ENST00000680963.1		c.2186A>T	p.Asp729Val	missense	Exon 12 of 12	ENSP00000505485.1	Q9H2J7-1
SLC6A15	ENST00000681106.1		c.2186A>T	p.Asp729Val	missense	Exon 13 of 13	ENSP00000505789.1	Q9H2J7-1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000248

AC:

AN:

241588

AF XY:

0.0000153

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000111

AC:

AN:

1438542

Hom.:

Cov.:

AF XY:

0.00000983

AC XY:

AN XY:

712066

show subpopulations

African (AFR)

AF:

0.000398

AC:

AN:

32680

American (AMR)

AF:

0.0000235

AC:

AN:

42560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24994

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.00

AC:

AN:

84476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096936

Other (OTH)

AF:

0.0000338

AC:

AN:

59136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000126

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.077

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.9

PhyloP100

4.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.45

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.15

Vest4

0.44

MVP

0.77

MPC

0.56

ClinPred

0.19

GERP RS

5.8

Varity_R

0.20

gMVP

0.76

Mutation Taster

=23/77

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over