rs2248829

Variant names:

• chr1-44002563-G-A
• rs2248829
• NM_001024845.3:c.807C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-44002563-G-A
• chr1-44002563-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001024845.3(SLC6A9):​c.807C>T​(p.Asp269Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 1,613,730 control chromosomes in the GnomAD database, including 8,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2030 hom., cov: 32)
  • Exomes 𝑓: 0.085 (6815 hom.)
• Consequence: SLC6A9 NM_001024845.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.26
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-44002563-G-A is Benign according to our data. Variant chr1-44002563-G-A is described in ClinVar as Benign. ClinVar VariationId is 1169776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 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.807C>T	p.Asp269Asp	synonymous	Exon 7 of 14	NP_001020016.1	P48067-2
	SLC6A9	NM_201649.4		c.1026C>T	p.Asp342Asp	synonymous	Exon 7 of 14	NP_964012.2	P48067-1
	SLC6A9	NM_006934.4		c.864C>T	p.Asp288Asp	synonymous	Exon 6 of 13	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.807C>T	p.Asp269Asp	synonymous	Exon 7 of 14	ENSP00000361384.4	P48067-2
	SLC6A9	ENST00000360584.6	TSL:1	c.1026C>T	p.Asp342Asp	synonymous	Exon 7 of 14	ENSP00000353791.2	P48067-1
	SLC6A9	ENST00000357730.6	TSL:1	c.864C>T	p.Asp288Asp	synonymous	Exon 6 of 13	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20880 AN: 151918 Hom.: 2024 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.128

GnomAD2 exomes AF: 0.112 AC: 28059 AN: 251478 AF XY: 0.106

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.0719

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.0713

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0853 AC: 124678 AN: 1461692 Hom.: 6815 Cov.: 33 AF XY: 0.0850 AC XY: 61808 AN XY: 727162

African (AFR) AF: 0.276 AC: 9225 AN: 33462

American (AMR) AF: 0.153 AC: 6864 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 1889 AN: 26132

East Asian (EAS) AF: 0.199 AC: 7907 AN: 39696

South Asian (SAS) AF: 0.115 AC: 9931 AN: 86248

European-Finnish (FIN) AF: 0.115 AC: 6121 AN: 53418

Middle Eastern (MID) AF: 0.139 AC: 804 AN: 5768

European-Non Finnish (NFE) AF: 0.0684 AC: 76009 AN: 1111852

Other (OTH) AF: 0.0982 AC: 5928 AN: 60394

GnomAD4 genome AF: 0.138 AC: 20923 AN: 152038 Hom.: 2030 Cov.: 32 AF XY: 0.139 AC XY: 10326 AN XY: 74344

African (AFR) AF: 0.269 AC: 11147 AN: 41450

American (AMR) AF: 0.128 AC: 1955 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.163 AC: 839 AN: 5154

South Asian (SAS) AF: 0.107 AC: 513 AN: 4812

European-Finnish (FIN) AF: 0.124 AC: 1313 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4564 AN: 67978

Other (OTH) AF: 0.127 AC: 267 AN: 2110

Alfa AF: 0.0938 Hom.: 3480

Bravo AF: 0.144

Asia WGS AF: 0.134 AC: 465 AN: 3478

EpiCase AF: 0.0671

EpiControl AF: 0.0689

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Atypical glycine encephalopathy (1)
-	-	1	SLC6A9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.65
DANN	Benign	0.89
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs2248829; hg19: chr1-44468235; COSMIC: COSV62211607;