rs2486001

chr1-44010315-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001024845.3(SLC6A9):c.188-219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 547,698 control chromosomes in the GnomAD database, including 197,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57363 hom., cov: 29)
  • Exomes 𝑓: 0.84 (140540 hom.)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.193

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-44010315-T-C is Benign according to our data. Variant chr1-44010315-T-C is described in ClinVar as [Benign]. Clinvar id is 1294943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3	c.188-219A>G		intron_variant		ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8	c.188-219A>G		intron_variant		5	NM_001024845.3	P1

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131622 AN: 151956 Hom.: 57318 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.841

GnomAD4 exome AF: 0.841 AC: 332726 AN: 395624 Hom.: 140540 Cov.: 4 AF XY: 0.837 AC XY: 173683 AN XY: 207468

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.763

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.903

Gnomad4 NFE exome AF: 0.855

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.866 AC: 131723 AN: 152074 Hom.: 57363 Cov.: 29 AF XY: 0.865 AC XY: 64294 AN XY: 74338

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.839

Alfa AF: 0.866 Hom.: 8621

Bravo AF: 0.861

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.2
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs2486001; hg19: chr1-44475987;