Variant rs61733181 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001024845.3(SLC6A9):c.960C>T(p.Tyr320=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00878 in 1,610,120 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 115 hom. )

Consequence

SLC6A9
NM_001024845.3 splice_region, synonymous

Scores

Splicing: ADA: 0.9521

Clinical Significance

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

Conservation

PhyloP100: 4.78

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-44002315-G-A is Benign according to our data. Variant chr1-44002315-G-A is described in ClinVar as [Benign]. Clinvar id is 476370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-44002315-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0112 (1713/152290) while in subpopulation SAS AF= 0.028 (135/4828). AF 95% confidence interval is 0.0241. There are 18 homozygotes in gnomad4. There are 870 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A9	NM_001024845.3 linkuse as main transcript	c.960C>T	p.Tyr320=	splice_region_variant, synonymous_variant	8/14	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.960C>T	p.Tyr320=	splice_region_variant, synonymous_variant	8/14	5	NM_001024845.3	ENSP00000361384	P1	P48067-2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1706

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00697

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00944

AC:

2373

AN:

251374

Hom.:

AF XY:

0.0104

AC XY:

1414

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0281

Gnomad FIN exome

AF:

0.00564

Gnomad NFE exome

AF:

0.00752

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00852

AC:

12425

AN:

1457830

Hom.:

115

Cov.:

AF XY:

0.00898

AC XY:

6511

AN XY:

725450

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.00522

Gnomad4 NFE exome

AF:

0.00740

Gnomad4 OTH exome

AF:

0.00933

GnomAD4 genome

AF:

0.0112

AC:

1713

AN:

152290

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

870

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0233

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0280

Gnomad4 FIN

AF:

0.00536

Gnomad4 NFE

AF:

0.00697

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00982

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Atypical glycine encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.52

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