rs2272383

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-8101952-G-A
• chr11-8101952-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177972.3(TUB):​c.*333G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 325,226 control chromosomes in the GnomAD database, including 49,887 homozygotes. 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: 𝑓 0.47 (20248 hom., cov: 33)
  • Exomes 𝑓: 0.57 (29639 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71210 AN: 152054 Hom.: 20251 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.573 AC: 99094 AN: 173054 Hom.: 29639 Cov.: 3 AF XY: 0.569 AC XY: 50552 AN XY: 88772

African (AFR) AF: 0.128 AC: 826 AN: 6446

American (AMR) AF: 0.461 AC: 3452 AN: 7494

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 3066 AN: 5264

East Asian (EAS) AF: 0.408 AC: 4730 AN: 11606

South Asian (SAS) AF: 0.467 AC: 6523 AN: 13960

European-Finnish (FIN) AF: 0.619 AC: 6809 AN: 11006

Middle Eastern (MID) AF: 0.577 AC: 473 AN: 820

European-Non Finnish (NFE) AF: 0.635 AC: 67265 AN: 106010

Other (OTH) AF: 0.569 AC: 5950 AN: 10448

GnomAD4 genome AF: 0.468 AC: 71199 AN: 152172 Hom.: 20248 Cov.: 33 AF XY: 0.471 AC XY: 34998 AN XY: 74384

African (AFR) AF: 0.138 AC: 5718 AN: 41538

American (AMR) AF: 0.489 AC: 7476 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2300 AN: 5170

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4820

European-Finnish (FIN) AF: 0.612 AC: 6476 AN: 10586

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42953 AN: 67984

Other (OTH) AF: 0.513 AC: 1084 AN: 2114

Alfa AF: 0.578 Hom.: 32983

Bravo AF: 0.442

Asia WGS AF: 0.435 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		3.4
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: rs2272383; hg19: chr11-8123499;