Genetic Variant ENST00000305253.8:c.8C>G (chr11-8038881-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000305253.8(TUB):c.8C>G(p.Ala3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TUB
ENST00000305253.8 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.0390

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

retinal dystrophy and obesity
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
essential tremor
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

TUB links:

ENSG00000254921 (HGNC:):

ENSG00000254921 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07553774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305253.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein
TUB	NM_003320.5	c.8C>G	p.Ala3Gly	missense	Exon 1 of 13	NP_003311.2
TUB	NM_001440538.1	c.56+19523C>G		intron	N/A	NP_001427467.1
TUB	NM_001440539.1	c.56+19523C>G		intron	N/A	NP_001427468.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUB	ENST00000305253.8	TSL:1	c.8C>G	p.Ala3Gly	missense	Exon 1 of 13	ENSP00000305426.4	P50607-2
TUB	ENST00000534099.5	TSL:2	c.56+19523C>G		intron	N/A	ENSP00000434400.1	E9PQR4
ENSG00000254921	ENST00000528151.1	TSL:4	n.305G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

TUB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.3

(source)

DANN

Benign

0.94

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.42

M_CAP

Benign

0.032

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.71

PhyloP100

-0.039

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.050

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Polyphen

0.0

Vest4

0.17

MutPred

0.083

Gain of methylation at R4 (P = 0.0712)

MVP

0.86

MPC

0.18

ClinPred

0.74

GERP RS

1.8

PromoterAI

-0.021

Neutral

(source)

gMVP

0.024

Mutation Taster

=99/1

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over