Genetic Variant TMUB1:p.Phe109Tyr (chr7-151082238-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136044.2(TMUB1):c.326T>A(p.Phe109Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,397,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMUB1
NM_001136044.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

Publications

0 publications found

Variant links:

Genes affected

TMUB1 (HGNC:21709): (transmembrane and ubiquitin like domain containing 1) Involved in ubiquitin-dependent ERAD pathway. Predicted to be located in several cellular components, including nucleolus; postsynaptic membrane; and recycling endosome. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMUB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136044.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMUB1	NM_001136044.2	MANE Select	c.326T>A	p.Phe109Tyr	missense	Exon 2 of 3	NP_001129516.1	Q9BVT8
	TMUB1	NM_031434.4		c.326T>A	p.Phe109Tyr	missense	Exon 2 of 3	NP_113622.1	Q9BVT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMUB1	ENST00000297533.9	TSL:1 MANE Select	c.326T>A	p.Phe109Tyr	missense	Exon 2 of 3	ENSP00000297533.4	Q9BVT8
TMUB1	ENST00000392818.7	TSL:1	c.326T>A	p.Phe109Tyr	missense	Exon 2 of 3	ENSP00000376565.3	Q9BVT8
TMUB1	ENST00000462940.1	TSL:1	c.326T>A	p.Phe109Tyr	missense	Exon 1 of 2	ENSP00000417519.1	Q9BVT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000500

AC:

AN:

199964

AF XY:

0.00000934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397044

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31160

American (AMR)

AF:

0.00

AC:

AN:

34960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21850

East Asian (EAS)

AF:

0.00

AC:

AN:

38270

South Asian (SAS)

AF:

0.00

AC:

AN:

76800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1079504

Other (OTH)

AF:

0.00

AC:

AN:

57572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.7

PhyloP100

7.1

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.32

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.66

MutPred

0.56

Loss of methylation at K108 (P = 0.028)

MVP

0.56

MPC

0.96

ClinPred

0.85

GERP RS

4.0

PromoterAI

0.0080

Neutral

(source)

Varity_R

0.34

gMVP

0.60

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over