3-119912701-TACCTA-T

Position:

• chr3-119912701-TACCTA-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001146156.2(GSK3B):​c.713_715+2delTAGGT​(p.Ile238_Asp239delinsAsn) variant causes a splice donor, disruptive inframe deletion, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GSK3B NM_001146156.2 splice_donor, disruptive_inframe_deletion, splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.91

Genes affected

GSK3B (HGNC:4617): (glycogen synthase kinase 3 beta) The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001146156.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSK3B	NM_001146156.2	c.713_715+2delTAGGT	p.Ile238_Asp239delinsAsn	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	6/11	ENST00000264235.13	NP_001139628.1
GSK3B	NM_002093.4	c.713_715+2delTAGGT	p.Ile238_Asp239delinsAsn	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	6/12		NP_002084.2
GSK3B	NM_001354596.2	c.713_715+2delTAGGT	p.Ile238_Asp239delinsAsn	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	6/10		NP_001341525.1
GSK3B	XM_006713610.4	c.713_715+2delTAGGT	p.Ile238_Asp239delinsAsn	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	6/11		XP_006713673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSK3B	ENST00000264235.13	c.713_715+2delTAGGT	p.Ile238_Asp239delinsAsn	splice_donor_variant, disruptive_inframe_deletion, splice_region_variant, intron_variant	6/11	1	NM_001146156.2	ENSP00000264235.9

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 27, 2022

Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-119631548;