1-43997498-G-A

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.*47C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,549,872 control chromosomes in the GnomAD database, including 7,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1595 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5899 hom.)
• Consequence: SLC6A9 NM_001024845.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.801

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=-0.75).
• BP6: Variant 1-43997498-G-A is Benign according to our data. Variant chr1-43997498-G-A is described in ClinVar as [Benign]. Clinvar id is 1242659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A9	NM_001024845.3	c.*47C>T		3_prime_UTR_variant	14/14	ENST00000372310.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A9	ENST00000372310.8	c.*47C>T		3_prime_UTR_variant	14/14	5	NM_001024845.3	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18940 AN: 152032 Hom.: 1591 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0960

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.106 AC: 25091 AN: 237020 Hom.: 1650 AF XY: 0.102 AC XY: 13199 AN XY: 129990

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.0713

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0708

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0825 AC: 115329 AN: 1397720 Hom.: 5899 Cov.: 24 AF XY: 0.0822 AC XY: 57420 AN XY: 698510

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0673

Gnomad4 OTH exome AF: 0.0933

GnomAD4 genome AF: 0.125 AC: 18965 AN: 152152 Hom.: 1595 Cov.: 32 AF XY: 0.126 AC XY: 9381 AN XY: 74386

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0934 Hom.: 238

Bravo AF: 0.130

Asia WGS AF: 0.119 AC: 413 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	-0.75
Cadd	Benign	13
Dann	Benign	0.77

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: rs2248253; hg19: chr1-44463170;