Variant 1-44002563-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001024845.3(SLC6A9):c.807C>T(p.Asp269Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 1,613,730 control chromosomes in the GnomAD database, including 8,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2030 hom., cov: 32)

Exomes 𝑓: 0.085 ( 6815 hom. )

Consequence

SLC6A9
NM_001024845.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.26

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:

SLC6A9 (HGNC:):

SLC6A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-44002563-G-A is Benign according to our data. Variant chr1-44002563-G-A is described in ClinVar as [Benign]. Clinvar id is 1169776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 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.807C>T	p.Asp269Asp	synonymous_variant	7/14	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.807C>T	p.Asp269Asp	synonymous_variant	7/14	5	NM_001024845.3	ENSP00000361384.4		P48067-2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20880

AN:

151918

Hom.:

2024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.0671

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.112

AC:

28059

AN:

251478

Hom.:

1987

AF XY:

0.106

AC XY:

14457

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.0719

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0853

AC:

124678

AN:

1461692

Hom.:

6815

Cov.:

AF XY:

0.0850

AC XY:

61808

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0723

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.0684

Gnomad4 OTH exome

AF:

0.0982

GnomAD4 genome

AF:

0.138

AC:

20923

AN:

152038

Hom.:

2030

Cov.:

AF XY:

0.139

AC XY:

10326

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0720

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.0671

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0853

Hom.:

1339

Bravo

AF:

0.144

Asia WGS

AF:

0.134

AC:

465

AN:

3478

EpiCase

AF:

0.0671

EpiControl

AF:

0.0689

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SLC6A9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 22, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Atypical glycine encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.65

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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