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. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.461

Gnomad4 ASJ exome AF: 0.582

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.569

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

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.513

Alfa AF: 0.599 Hom.: 26127

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272383; hg19: chr11-8123499;