rs2286245

chr1-43997532-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001024845.3(SLC6A9):c.*13G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,611,184 control chromosomes in the GnomAD database, including 1,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (141 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1684 hom.)
• Consequence: SLC6A9 NM_001024845.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 1-43997532-C-T is Benign according to our data. Variant chr1-43997532-C-T is described in ClinVar as [Benign]. Clinvar id is 1240974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3	c.*13G>A		3_prime_UTR_variant	14/14	ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8	c.*13G>A		3_prime_UTR_variant	14/14	5	NM_001024845.3	P1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5753 AN: 152102 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0483

GnomAD3 exomes AF: 0.0488 AC: 11986 AN: 245450 Hom.: 409 AF XY: 0.0498 AC XY: 6643 AN XY: 133394

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.0631

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0370

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0422 AC: 61548 AN: 1458964 Hom.: 1684 Cov.: 32 AF XY: 0.0433 AC XY: 31423 AN XY: 725944

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.0607

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0776

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.0379

Gnomad4 OTH exome AF: 0.0443

GnomAD4 genome AF: 0.0379 AC: 5763 AN: 152220 Hom.: 141 Cov.: 32 AF XY: 0.0389 AC XY: 2894 AN XY: 74430

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0603

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0762

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0386 Hom.: 116

Bravo AF: 0.0380

Asia WGS AF: 0.105 AC: 365 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	-0.24
Cadd	Benign	14
Dann	Benign	0.92

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: rs2286245; hg19: chr1-44463204;