6-29556081-TG-CC

Variant names:

• chr6-29556081-TG-CC
• NM_006398.4:c.296_297delCAinsGG
• UBD p.Ala99Gly

Variant summary

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

The NM_006398.4(UBD):​c.296_297delCAinsGG​(p.Ala99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBD NM_006398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

UBD (HGNC:18795): (ubiquitin D) This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types. [provided by RefSeq, Aug 2017]

OR2I1 (HGNC:8258): (olfactory receptor family 2 subfamily I member 1 pseudogene) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with language delay and variable cognitive abnormalities

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006398.4. 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
	UBD	NM_006398.4	MANE Select	c.296_297delCAinsGG	p.Ala99Gly	missense	N/A	NP_006389.2	O15205
	OR2I1	NM_001396058.1	MANE Select	c.*1915_*1916delTGinsCC		3_prime_UTR	Exon 2 of 2	NP_001382987.1	Q8NGU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBD	ENST00000377050.5	TSL:1 MANE Select	c.296_297delCAinsGG	p.Ala99Gly	missense	N/A	ENSP00000366249.4	O15205
	OR2I1	ENST00000641137.2	MANE Select	c.*1915_*1916delTGinsCC		3_prime_UTR	Exon 2 of 2	ENSP00000493715.1	Q8NGU4
	UBD	ENST00000866140.1		c.440_441delCAinsGG	p.Ala147Gly	missense	N/A	ENSP00000536199.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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: chr6-29523858;