rs2486001

Variant names:

• chr1-44010315-T-C
• rs2486001
• NM_001024845.3:c.188-219A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-44010315-T-C
• chr1-44010315-T-A
• chr1-44010315-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001024845.3(SLC6A9):​c.188-219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 547,698 control chromosomes in the GnomAD database, including 197,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57363 hom., cov: 29)
  • Exomes 𝑓: 0.84 (140540 hom.)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.193
• Publications: 13 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: Unknown, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-44010315-T-C is Benign according to our data. Variant chr1-44010315-T-C is described in ClinVar as Benign. ClinVar VariationId is 1294943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A9	NM_001024845.3	MANE Select	c.188-219A>G		intron	N/A	NP_001020016.1	P48067-2
	SLC6A9	NM_201649.4		c.407-219A>G		intron	N/A	NP_964012.2	P48067-1
	SLC6A9	NM_006934.4		c.245-219A>G		intron	N/A	NP_008865.2	P48067-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A9	ENST00000372310.8	TSL:5 MANE Select	c.188-219A>G		intron	N/A	ENSP00000361384.4	P48067-2
	SLC6A9	ENST00000360584.6	TSL:1	c.407-219A>G		intron	N/A	ENSP00000353791.2	P48067-1
	SLC6A9	ENST00000357730.6	TSL:1	c.245-219A>G		intron	N/A	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131622 AN: 151956 Hom.: 57318 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.841

GnomAD4 exome AF: 0.841 AC: 332726 AN: 395624 Hom.: 140540 Cov.: 4 AF XY: 0.837 AC XY: 173683 AN XY: 207468

African (AFR) AF: 0.934 AC: 10719 AN: 11474

American (AMR) AF: 0.760 AC: 12344 AN: 16240

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 9397 AN: 12216

East Asian (EAS) AF: 0.763 AC: 20722 AN: 27160

South Asian (SAS) AF: 0.803 AC: 33046 AN: 41136

European-Finnish (FIN) AF: 0.903 AC: 22785 AN: 25234

Middle Eastern (MID) AF: 0.795 AC: 1408 AN: 1770

European-Non Finnish (NFE) AF: 0.855 AC: 203080 AN: 237434

Other (OTH) AF: 0.837 AC: 19225 AN: 22960

GnomAD4 genome AF: 0.866 AC: 131723 AN: 152074 Hom.: 57363 Cov.: 29 AF XY: 0.865 AC XY: 64294 AN XY: 74338

African (AFR) AF: 0.934 AC: 38766 AN: 41508

American (AMR) AF: 0.772 AC: 11789 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4037 AN: 5152

South Asian (SAS) AF: 0.793 AC: 3809 AN: 4806

European-Finnish (FIN) AF: 0.910 AC: 9636 AN: 10586

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58255 AN: 67964

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.859 Hom.: 83080

Bravo AF: 0.861

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.2
DANN	Benign	0.87
PhyloP100		-0.19
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: rs2486001; hg19: chr1-44475987;