11-8101952-G-C

Variant names:

• chr11-8101952-G-C
• rs2272383
• NM_177972.3:c.*333G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177972.3(TUB):​c.*333G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TUB NM_177972.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• Publications: 11 publications found

Genes affected

TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

RIC3 (HGNC:30338): (RIC3 acetylcholine receptor chaperone) This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

RIC3 Gene-Disease associations (from GenCC):

• Parkinson disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• movement disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUB	NM_177972.3	c.*333G>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000299506.3	NP_813977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000299506.3	c.*333G>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_177972.3	ENSP00000299506.3
TUB	ENST00000305253.8	c.*333G>C		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000305426.4
TUB	ENST00000534099.5	c.*333G>C		downstream_gene_variant		2		ENSP00000434400.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 173796 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 89164

African (AFR) AF: 0.00 AC: 0 AN: 6464

American (AMR) AF: 0.00 AC: 0 AN: 7512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5286

East Asian (EAS) AF: 0.00 AC: 0 AN: 11662

South Asian (SAS) AF: 0.00 AC: 0 AN: 14032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 826

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106468

Other (OTH) AF: 0.00 AC: 0 AN: 10494

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 32983

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		3.4

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: rs2272383; hg19: chr11-8123499;