Genetic Variant ENST00000305253.8:c.204-21158T>C (chr11-8068452-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000305253.8(TUB):c.204-21158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,160 control chromosomes in the GnomAD database, including 16,271 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 0.46 ( 16244 hom., cov: 32)

Exomes 𝑓: 0.48 ( 27 hom. )

Consequence

TUB
ENST00000305253.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.434

Publications

3 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 links:

TUB-AS1 (HGNC:51120): (TUB antisense RNA 1)

TUB-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000305253.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

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	Effect	Exon Rank	Protein
TUB	NM_003320.5	c.204-21158T>C	intron	N/A	NP_003311.2
TUB	NM_001440538.1	c.57-21158T>C	intron	N/A	NP_001427467.1
TUB	NM_001440539.1	c.57-21158T>C	intron	N/A	NP_001427468.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TUB	ENST00000305253.8	TSL:1	c.204-21158T>C	intron	N/A	ENSP00000305426.4	P50607-2
TUB	ENST00000534099.5	TSL:2	c.57-21158T>C	intron	N/A	ENSP00000434400.1	E9PQR4
TUB-AS1	ENST00000506601.1	TSL:2	n.1100T>C	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69383

AN:

151830

Hom.:

16241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.481

AC:

102

AN:

212

Hom.:

Cov.:

AF XY:

0.473

AC XY:

AN XY:

146

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.513

AC:

AN:

154

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.457

AC:

69405

AN:

151948

Hom.:

16244

Cov.:

AF XY:

0.451

AC XY:

33500

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.527

AC:

21834

AN:

41428

American (AMR)

AF:

0.334

AC:

5097

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1231

AN:

3470

East Asian (EAS)

AF:

0.461

AC:

2373

AN:

5150

South Asian (SAS)

AF:

0.472

AC:

2271

AN:

4816

European-Finnish (FIN)

AF:

0.464

AC:

4908

AN:

10574

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30357

AN:

67936

Other (OTH)

AF:

0.418

AC:

879

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1932

3864

5796

7728

9660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

644

1288

1932

2576

3220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.444

Hom.:

64048

Bravo

AF:

0.452

Asia WGS

AF:

0.446

AC:

1549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.0

(source)

DANN

Benign

0.70

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over