Variant 7-151082472-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000297533.9(TMUB1):c.92C>T(p.Thr31Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,445,294 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: 0.0000014 ( 0 hom. )

Consequence

TMUB1
ENST00000297533.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMUB1	NM_001136044.2 linkuse as main transcript	c.92C>T	p.Thr31Met	missense_variant	2/3	ENST00000297533.9	NP_001129516.1
TMUB1	NM_031434.4 linkuse as main transcript	c.92C>T	p.Thr31Met	missense_variant	2/3		NP_113622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMUB1	ENST00000297533.9 linkuse as main transcript	c.92C>T	p.Thr31Met	missense_variant	2/3	1	NM_001136044.2	ENSP00000297533	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445294

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.92C>T (p.T31M) alteration is located in exon 2 (coding exon 1) of the TMUB1 gene. This alteration results from a C to T substitution at nucleotide position 92, causing the threonine (T) at amino acid position 31 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;T;T;T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

.;.;.;.;D;D;D

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

M;M;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.0

D;D;D;D;D;D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;.;D

Polyphen

0.96

P;P;P;P;P;.;.

Vest4

0.75

MutPred

0.33

Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);Gain of catalytic residue at T31 (P = 0.0028);

MVP

0.68

MPC

0.94

ClinPred

0.99

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.84

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over