1-43998533-A-G

Variant names:

• chr1-43998533-A-G
• rs3791124
• NM_001024845.3:c.1537-508T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A9	NM_001024845.3	MANE Select	c.1537-508T>C		intron	N/A	NP_001020016.1
	SLC6A9	NM_201649.4		c.1756-508T>C		intron	N/A	NP_964012.2
	SLC6A9	NM_006934.4		c.1594-508T>C		intron	N/A	NP_008865.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A9	ENST00000372310.8	TSL:5 MANE Select	c.1537-508T>C		intron	N/A	ENSP00000361384.4
	SLC6A9	ENST00000360584.6	TSL:1	c.1756-508T>C		intron	N/A	ENSP00000353791.2
	SLC6A9	ENST00000357730.6	TSL:1	c.1594-508T>C		intron	N/A	ENSP00000350362.2

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

African (AFR) AF: 0.933 AC: 38759 AN: 41548

American (AMR) AF: 0.764 AC: 11680 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3466

East Asian (EAS) AF: 0.783 AC: 4038 AN: 5158

South Asian (SAS) AF: 0.798 AC: 3850 AN: 4826

European-Finnish (FIN) AF: 0.907 AC: 9621 AN: 10604

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57711 AN: 68004

Other (OTH) AF: 0.826 AC: 1745 AN: 2112

Alfa AF: 0.850 Hom.: 28853

Bravo AF: 0.855

Asia WGS AF: 0.789 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs3791124; hg19: chr1-44464205;