rs16935797

chr11-8099753-T-Cchr11-8099753-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177972.3(TUB):c.1117-750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,172 control chromosomes in the GnomAD database, including 1,808 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 0.15 (1808 hom., cov: 33)
• Consequence: TUB NM_177972.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TUB	NM_177972.3	c.1117-750T>C		intron_variant		ENST00000299506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUB	ENST00000299506.3	c.1117-750T>C		intron_variant		1	NM_177972.3	P1
TUB	ENST00000305253.8	c.1282-750T>C		intron_variant		1
TUB	ENST00000534099.5	c.1135-750T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22534 AN: 152054 Hom.: 1803 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22563 AN: 152172 Hom.: 1808 Cov.: 33 AF XY: 0.148 AC XY: 11029 AN XY: 74394

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0908

Gnomad4 EAS AF: 0.0828

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.102

Alfa AF: 0.130 Hom.: 807

Bravo AF: 0.146

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.085
Dann	Benign	0.79

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: rs16935797; hg19: chr11-8121300;