11-8089993-T-C

Variant names:

• chr11-8089993-T-C
• rs2272382
• NM_177972.3:c.91-76T>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.91-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,477,852 control chromosomes in the GnomAD database, including 330,398 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 0.64 (31299 hom., cov: 35)
  • Exomes 𝑓: 0.67 (299099 hom.)
• Consequence: TUB NM_177972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 7 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]

TUB Gene-Disease associations (from GenCC):

• retinal dystrophy and obesity

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• essential tremor

  Inheritance: AD 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUB	NM_177972.3	c.91-76T>C		intron_variant	Intron 2 of 11	ENST00000299506.3	NP_813977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000299506.3	c.91-76T>C		intron_variant	Intron 2 of 11	1	NM_177972.3	ENSP00000299506.3
TUB	ENST00000305253.8	c.256-76T>C		intron_variant	Intron 3 of 12	1		ENSP00000305426.4
TUB	ENST00000534099.5	c.109-76T>C		intron_variant	Intron 2 of 11	2		ENSP00000434400.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 97045 AN: 152062 Hom.: 31292 Cov.: 35

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.670 AC: 888682 AN: 1325672 Hom.: 299099 AF XY: 0.669 AC XY: 431898 AN XY: 645854

African (AFR) AF: 0.565 AC: 16536 AN: 29270

American (AMR) AF: 0.524 AC: 13519 AN: 25820

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 13190 AN: 20290

East Asian (EAS) AF: 0.622 AC: 21872 AN: 35188

South Asian (SAS) AF: 0.584 AC: 39002 AN: 66784

European-Finnish (FIN) AF: 0.665 AC: 30287 AN: 45548

Middle Eastern (MID) AF: 0.669 AC: 3050 AN: 4556

European-Non Finnish (NFE) AF: 0.685 AC: 714747 AN: 1043536

Other (OTH) AF: 0.667 AC: 36479 AN: 54680

GnomAD4 genome AF: 0.638 AC: 97085 AN: 152180 Hom.: 31299 Cov.: 35 AF XY: 0.637 AC XY: 47394 AN XY: 74406

African (AFR) AF: 0.572 AC: 23730 AN: 41522

American (AMR) AF: 0.574 AC: 8781 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2295 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3353 AN: 5160

South Asian (SAS) AF: 0.613 AC: 2961 AN: 4832

European-Finnish (FIN) AF: 0.671 AC: 7109 AN: 10602

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.687 AC: 46669 AN: 67970

Other (OTH) AF: 0.639 AC: 1349 AN: 2112

Alfa AF: 0.655 Hom.: 4072

Bravo AF: 0.630

Asia WGS AF: 0.612 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.74
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272382; hg19: chr11-8111540;