SLC6A9 p.Tyr320Tyr

Variant names:

• chr1-44002314-G-G
• NM_001024845.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-44002315--
• chr1-44002315-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001024845.3(SLC6A9):​c. variant causes a splice region, exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC6A9 NM_001024845.3 splice_region, exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.78
• Publications: 0 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		splice_region exon_region	Exon 8 of 14	NP_001020016.1	P48067-2
	SLC6A9	NM_201649.4		c.		splice_region exon_region	Exon 8 of 14	NP_964012.2	P48067-1
	SLC6A9	NM_006934.4		c.		splice_region exon_region	Exon 7 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.		splice_region exon_region	Exon 8 of 14	ENSP00000361384.4	P48067-2
	SLC6A9	ENST00000360584.6	TSL:1	c.		splice_region exon_region	Exon 8 of 14	ENSP00000353791.2	P48067-1
	SLC6A9	ENST00000357730.6	TSL:1	c.		splice_region exon_region	Exon 7 of 13	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-44467986;