Genetic Variant TMUB1:p.Arg174Lys (chr7-151081769-C-T) – 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 NM_001136044.2(TMUB1):c.521G>A(p.Arg174Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,594,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 1.69

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07789579).

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.521G>A	p.Arg174Lys	missense	Exon 3 of 3	NP_001129516.1	Q9BVT8
	TMUB1	NM_031434.4		c.521G>A	p.Arg174Lys	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.521G>A	p.Arg174Lys	missense	Exon 3 of 3	ENSP00000297533.4	Q9BVT8
TMUB1	ENST00000392818.7	TSL:1	c.521G>A	p.Arg174Lys	missense	Exon 3 of 3	ENSP00000376565.3	Q9BVT8
TMUB1	ENST00000462940.1	TSL:1	c.521G>A	p.Arg174Lys	missense	Exon 2 of 2	ENSP00000417519.1	Q9BVT8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1442874

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

715584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33352

American (AMR)

AF:

0.00

AC:

AN:

41062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25554

East Asian (EAS)

AF:

0.0000512

AC:

AN:

39050

South Asian (SAS)

AF:

0.00

AC:

AN:

83208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104146

Other (OTH)

AF:

0.00

AC:

AN:

59820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.011

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.66

M_CAP

Benign

0.021

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.7

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.27

REVEL

Benign

0.15

Sift

Benign

0.79

Sift4G

Benign

1.0

Polyphen

0.63

Vest4

0.17

MutPred

0.18

Gain of ubiquitination at R174 (P = 0.0054)

MVP

0.19

MPC

0.92

ClinPred

0.77

GERP RS

4.0

Varity_R

0.11

gMVP

0.42

Mutation Taster

=96/4

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over