1-43998533-A-G

Position:

• chr1-43998533-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024845.3(SLC6A9):​c.1537-508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,204 control chromosomes in the GnomAD database, including 56,712 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 0.86 (56712 hom., cov: 32)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A9	NM_001024845.3	c.1537-508T>C		intron_variant		ENST00000372310.8	NP_001020016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A9	ENST00000372310.8	c.1537-508T>C		intron_variant		5	NM_001024845.3	ENSP00000361384.4

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130896 AN: 152086 Hom.: 56665 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.861 AC: 131000 AN: 152204 Hom.: 56712 Cov.: 32 AF XY: 0.860 AC XY: 63967 AN XY: 74398

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.826

Alfa AF: 0.851 Hom.: 26089

Bravo AF: 0.855

Asia WGS AF: 0.789 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3791124; hg19: chr1-44464205;