11-8089993-T-C

Position:

• chr11-8089993-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TUB	NM_177972.3	c.91-76T>C		intron_variant		ENST00000299506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUB	ENST00000299506.3	c.91-76T>C		intron_variant		1	NM_177972.3	P1
TUB	ENST00000305253.8	c.256-76T>C		intron_variant		1
TUB	ENST00000534099.5	c.109-76T>C		intron_variant		2

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

Gnomad4 AFR exome AF: 0.565

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.622

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.667

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

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.639

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272382; hg19: chr11-8111540;