rs783307

Variant names:

• chr1-44028880-T-C
• rs783307
• NM_001024845.3:c.-86+2426A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-44028880-T-C
• chr1-44028880-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024845.3(SLC6A9):​c.-86+2426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,232 control chromosomes in the GnomAD database, including 2,854 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2854 hom., cov: 32)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• atypical glycine encephalopathy

  Inheritance: AR, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A9	NM_001024845.3	c.-86+2426A>G		intron_variant	Intron 1 of 13	ENST00000372310.8	NP_001020016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A9	ENST00000372310.8	c.-86+2426A>G		intron_variant	Intron 1 of 13	5	NM_001024845.3	ENSP00000361384.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27186 AN: 151114 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27233 AN: 151232 Hom.: 2854 Cov.: 32 AF XY: 0.182 AC XY: 13457 AN XY: 73852

African (AFR) AF: 0.182 AC: 7472 AN: 41096

American (AMR) AF: 0.245 AC: 3732 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3464

East Asian (EAS) AF: 0.442 AC: 2274 AN: 5142

South Asian (SAS) AF: 0.252 AC: 1211 AN: 4798

European-Finnish (FIN) AF: 0.110 AC: 1150 AN: 10446

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.147 AC: 9931 AN: 67736

Other (OTH) AF: 0.192 AC: 402 AN: 2096

Alfa AF: 0.167 Hom.: 1364

Bravo AF: 0.187

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.64
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs783307; hg19: chr1-44494552;