Variant rs2248632 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001024845.3(SLC6A9):c.1435+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 1,601,346 control chromosomes in the GnomAD database, including 8,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1746 hom., cov: 33)

Exomes 𝑓: 0.084 ( 6408 hom. )

Consequence

SLC6A9
NM_001024845.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

SLC6A9 (HGNC:11056): (solute carrier family 6 member 9) The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]

SLC6A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016821086).

BP6

Variant 1-44000934-G-A is Benign according to our data. Variant chr1-44000934-G-A is described in ClinVar as [Benign]. Clinvar id is 1179904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A9	NM_001024845.3 linkuse as main transcript	c.1435+22C>T		intron_variant		ENST00000372310.8	NP_001020016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A9	ENST00000372310.8 linkuse as main transcript	c.1435+22C>T		intron_variant		5	NM_001024845.3	ENSP00000361384	P1	P48067-2

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19666

AN:

152118

Hom.:

1739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0669

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.108

AC:

26380

AN:

243626

Hom.:

1797

AF XY:

0.104

AC XY:

13603

AN XY:

131424

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0691

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.0703

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0840

AC:

121657

AN:

1449108

Hom.:

6408

Cov.:

AF XY:

0.0837

AC XY:

60256

AN XY:

719804

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.0680

Gnomad4 OTH exome

AF:

0.0961

GnomAD4 genome

AF:

0.129

AC:

19709

AN:

152238

Hom.:

1746

Cov.:

AF XY:

0.131

AC XY:

9753

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.0720

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.0669

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.111

Hom.:

413

Bravo

AF:

0.135

TwinsUK

AF:

0.0650

AC:

241

ALSPAC

AF:

0.0682

AC:

263

ESP6500AA

AF:

0.235

AC:

1036

ESP6500EA

AF:

0.0656

AC:

564

ExAC

AF:

0.109

AC:

13278

Asia WGS

AF:

0.133

AC:

461

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.53

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PROVEAN

Benign

0.74

REVEL

Benign

0.11

Sift

Benign

0.031

Sift4G

Uncertain

0.0040

Vest4

0.096

ClinPred

0.0031

GERP RS

3.3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over