rs1766967

chr1-44009914-G-Achr1-44009914-G-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.319+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 1,594,426 control chromosomes in the GnomAD database, including 7,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1409 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6138 hom.)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.620

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=-0.81).
• BP6: Variant 1-44009914-G-A is Benign according to our data. Variant chr1-44009914-G-A is described in ClinVar as [Benign]. Clinvar id is 1232090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3	c.319+51C>T		intron_variant		ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8	c.319+51C>T		intron_variant		5	NM_001024845.3	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18238 AN: 152092 Hom.: 1407 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.109 AC: 25989 AN: 239514 Hom.: 1708 AF XY: 0.104 AC XY: 13506 AN XY: 129380

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.0737

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0714

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0834 AC: 120224 AN: 1442214 Hom.: 6138 Cov.: 30 AF XY: 0.0833 AC XY: 59627 AN XY: 715996

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.0729

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0940

GnomAD4 genome AF: 0.120 AC: 18256 AN: 152212 Hom.: 1409 Cov.: 32 AF XY: 0.121 AC XY: 9035 AN XY: 74412

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0759 Hom.: 971

Bravo AF: 0.125

Asia WGS AF: 0.129 AC: 448 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 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.5
Dann	Benign	0.54

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: rs1766967; hg19: chr1-44475586; COSMIC: COSV62212276; COSMIC: COSV62212276;