Genetic Variant TMUB1:p.Tyr212Cys (chr7-151081655-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001136044.2(TMUB1):c.635A>G(p.Tyr212Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMUB1
NM_001136044.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

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.635A>G	p.Tyr212Cys	missense	Exon 3 of 3	NP_001129516.1	Q9BVT8
	TMUB1	NM_031434.4		c.635A>G	p.Tyr212Cys	missense	Exon 3 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.635A>G	p.Tyr212Cys	missense	Exon 3 of 3	ENSP00000297533.4	Q9BVT8
TMUB1	ENST00000392818.7	TSL:1	c.635A>G	p.Tyr212Cys	missense	Exon 3 of 3	ENSP00000376565.3	Q9BVT8
TMUB1	ENST00000462940.1	TSL:1	c.635A>G	p.Tyr212Cys	missense	Exon 2 of 2	ENSP00000417519.1	Q9BVT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000465

AC:

AN:

214928

AF XY:

0.00

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:

6.92e-7

AC:

AN:

1445130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33362

American (AMR)

AF:

0.00

AC:

AN:

42360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39246

South Asian (SAS)

AF:

0.00

AC:

AN:

84158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5528

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104342

Other (OTH)

AF:

0.00

AC:

AN:

59700

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

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000832

AC:

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

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.1

PhyloP100

5.9

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MutPred

0.28

Loss of catalytic residue at L207 (P = 0.0762)

MVP

0.52

MPC

1.0

ClinPred

1.0

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.90

gMVP

0.94

Mutation Taster

=59/41

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over