rs2286245

Variant names:

• chr1-43997532-C-T
• rs2286245
• NM_001024845.3:c.*13G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-43997532-C-T
• chr1-43997532-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001024845.3(SLC6A9):​c.*13G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 1,611,184 control chromosomes in the GnomAD database, including 1,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (141 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1684 hom.)
• Consequence: SLC6A9 NM_001024845.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.19
• Publications: 9 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 1-43997532-C-T is Benign according to our data. Variant chr1-43997532-C-T is described in ClinVar as Benign. ClinVar VariationId is 1240974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.*13G>A		3_prime_UTR	Exon 14 of 14	NP_001020016.1	P48067-2
	SLC6A9	NM_201649.4		c.*13G>A		3_prime_UTR	Exon 14 of 14	NP_964012.2	P48067-1
	SLC6A9	NM_006934.4		c.*13G>A		3_prime_UTR	Exon 13 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.*13G>A		3_prime_UTR	Exon 14 of 14	ENSP00000361384.4	P48067-2
	SLC6A9	ENST00000360584.6	TSL:1	c.*13G>A		3_prime_UTR	Exon 14 of 14	ENSP00000353791.2	P48067-1
	SLC6A9	ENST00000357730.6	TSL:1	c.*13G>A		3_prime_UTR	Exon 13 of 13	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5753 AN: 152102 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0488 AC: 11986 AN: 245450 AF XY: 0.0498

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.0631

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0370

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0422 AC: 61548 AN: 1458964 Hom.: 1684 Cov.: 32 AF XY: 0.0433 AC XY: 31423 AN XY: 725944

African (AFR) AF: 0.0162 AC: 542 AN: 33416

American (AMR) AF: 0.0607 AC: 2703 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 478 AN: 26070

East Asian (EAS) AF: 0.128 AC: 5082 AN: 39676

South Asian (SAS) AF: 0.0776 AC: 6684 AN: 86184

European-Finnish (FIN) AF: 0.0208 AC: 1098 AN: 52676

Middle Eastern (MID) AF: 0.0298 AC: 168 AN: 5638

European-Non Finnish (NFE) AF: 0.0379 AC: 42124 AN: 1110456

Other (OTH) AF: 0.0443 AC: 2669 AN: 60282

GnomAD4 genome AF: 0.0379 AC: 5763 AN: 152220 Hom.: 141 Cov.: 32 AF XY: 0.0389 AC XY: 2894 AN XY: 74430

African (AFR) AF: 0.0186 AC: 774 AN: 41528

American (AMR) AF: 0.0603 AC: 922 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.117 AC: 605 AN: 5160

South Asian (SAS) AF: 0.0762 AC: 367 AN: 4814

European-Finnish (FIN) AF: 0.0185 AC: 196 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2649 AN: 68004

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0380 Hom.: 171

Bravo AF: 0.0380

Asia WGS AF: 0.105 AC: 365 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	-0.24
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		2.2
Mutation Taster		=92/8	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: rs2286245; hg19: chr1-44463204; COSMIC: COSV107437661; COSMIC: COSV107437661;