Variant chr11-8038866-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_003320.5(TUB):c.-8T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,682 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

TUB
NM_003320.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.658

Variant links:

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 links:

ENSG00000254921 (HGNC:):

ENSG00000254921 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000657 (100/152266) while in subpopulation NFE AF= 0.00113 (77/68010). AF 95% confidence interval is 0.000928. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
TUB	NM_003320.5 linkuse as main transcript	c.-8T>G	5_prime_UTR_variant	1/13	NP_003311.2	P50607-2
TUB	XM_005253109.4 linkuse as main transcript	c.164+19508T>G	intron_variant		XP_005253166.1
TUB	XM_047427512.1 linkuse as main transcript	c.164+19508T>G	intron_variant		XP_047283468.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
TUB	ENST00000305253 linkuse as main transcript	c.-8T>G	5_prime_UTR_variant	1/13	1	ENSP00000305426.4	P50607-2
TUB	ENST00000534099.5 linkuse as main transcript	c.56+19508T>G	intron_variant		2	ENSP00000434400.1	E9PQR4
ENSG00000254921	ENST00000528151.1 linkuse as main transcript	n.320A>C	non_coding_transcript_exon_variant	2/2	4
ENSG00000254921	ENST00000526646.2 linkuse as main transcript	n.202+651A>C	intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000661

AC:

166

AN:

250998

Hom.:

AF XY:

0.000774

AC XY:

105

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00106

AC:

1553

AN:

1461416

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

770

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152266

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000890

Hom.:

Bravo

AF:

0.000650

EpiCase

AF:

0.00164

EpiControl

AF:

0.00160

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.4

DANN

Benign

0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over