1-44009914-G-A

Variant names:

• chr1-44009914-G-A
• rs1766967
• NM_001024845.3:c.319+51C>T

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.319+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 1,594,426 control chromosomes in the GnomAD database, including 7,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1409 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6138 hom.)
• Consequence: SLC6A9 NM_001024845.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620
• Publications: 14 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=-0.81).
• BP6: Variant 1-44009914-G-A is Benign according to our data. Variant chr1-44009914-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 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.319+51C>T		intron	N/A	NP_001020016.1	P48067-2
	SLC6A9	NM_201649.4		c.538+51C>T		intron	N/A	NP_964012.2	P48067-1
	SLC6A9	NM_006934.4		c.376+51C>T		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.319+51C>T		intron	N/A	ENSP00000361384.4	P48067-2
	SLC6A9	ENST00000360584.6	TSL:1	c.538+51C>T		intron	N/A	ENSP00000353791.2	P48067-1
	SLC6A9	ENST00000357730.6	TSL:1	c.376+51C>T		intron	N/A	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18238 AN: 152092 Hom.: 1407 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.109 AC: 25989 AN: 239514 AF XY: 0.104

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.0737

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0714

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0834 AC: 120224 AN: 1442214 Hom.: 6138 Cov.: 30 AF XY: 0.0833 AC XY: 59627 AN XY: 715996

African (AFR) AF: 0.212 AC: 6932 AN: 32768

American (AMR) AF: 0.150 AC: 6460 AN: 42970

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 1824 AN: 25036

East Asian (EAS) AF: 0.204 AC: 8035 AN: 39402

South Asian (SAS) AF: 0.115 AC: 9644 AN: 83820

European-Finnish (FIN) AF: 0.114 AC: 6018 AN: 52614

Middle Eastern (MID) AF: 0.132 AC: 694 AN: 5256

European-Non Finnish (NFE) AF: 0.0682 AC: 75038 AN: 1100986

Other (OTH) AF: 0.0940 AC: 5579 AN: 59362

GnomAD4 genome AF: 0.120 AC: 18256 AN: 152212 Hom.: 1409 Cov.: 32 AF XY: 0.121 AC XY: 9035 AN XY: 74412

African (AFR) AF: 0.206 AC: 8562 AN: 41518

American (AMR) AF: 0.122 AC: 1865 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3470

East Asian (EAS) AF: 0.168 AC: 866 AN: 5152

South Asian (SAS) AF: 0.106 AC: 512 AN: 4828

European-Finnish (FIN) AF: 0.125 AC: 1323 AN: 10600

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4557 AN: 68024

Other (OTH) AF: 0.115 AC: 242 AN: 2112

Alfa AF: 0.0870 Hom.: 2184

Bravo AF: 0.125

Asia WGS AF: 0.129 AC: 448 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	-0.81
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		0.62
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: rs1766967; hg19: chr1-44475586; COSMIC: COSV62212276; COSMIC: COSV62212276;