Variant 1-43998031-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001024845.3(SLC6A9):c.1537-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,607,960 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

SLC6A9
NM_001024845.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007098

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-43998031-C-T is Benign according to our data. Variant chr1-43998031-C-T is described in ClinVar as [Benign]. Clinvar id is 476371.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00243 (370/152280) while in subpopulation AFR AF= 0.00794 (330/41560). AF 95% confidence interval is 0.00724. There are 3 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3 linkuse as main transcript	c.1537-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8 linkuse as main transcript	c.1537-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001024845.3	P1	P48067-2

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000680

AC:

167

AN:

245686

Hom.:

AF XY:

0.000528

AC XY:

AN XY:

132598

show subpopulations

Gnomad AFR exome

AF:

0.00698

Gnomad AMR exome

AF:

0.000702

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0000675

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000323

AC:

470

AN:

1455680

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

210

AN XY:

723530

show subpopulations

Gnomad4 AFR exome

AF:

0.00644

Gnomad4 AMR exome

AF:

0.000834

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.0000936

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.000865

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152280

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00794

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000677

Hom.:

Bravo

AF:

0.00253

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atypical glycine encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -16

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