Variant 7-151082238-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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:

Genome browser will be placed here

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.326T>A	p.Phe109Tyr	missense_variant	2/3	ENST00000297533.9	NP_001129516.1	Q9BVT8A0A090N8Q3
TMUB1	NM_031434.4 linkuse as main transcript	c.326T>A	p.Phe109Tyr	missense_variant	2/3		NP_113622.1	Q9BVT8A0A090N8Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMUB1	ENST00000297533.9 linkuse as main transcript	c.326T>A	p.Phe109Tyr	missense_variant	2/3	1	NM_001136044.2	ENSP00000297533.4		Q9BVT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000500

AC:

AN:

199964

Hom.:

AF XY:

0.00000934

AC XY:

AN XY:

107074

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 29, 2023

The c.326T>A (p.F109Y) alteration is located in exon 2 (coding exon 1) of the TMUB1 gene. This alteration results from a T to A substitution at nucleotide position 326, causing the phenylalanine (F) at amino acid position 109 to be replaced by a tyrosine (Y). 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

Benign

0.33

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

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

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

.;.;.;.;T;D;T

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.45

T;T;T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.7

L;L;L;L;L;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.010

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

Sift4G

Pathogenic

0.0

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

Polyphen

1.0

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

Vest4

0.66

MutPred

0.56

Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);Loss of methylation at K108 (P = 0.028);

MVP

0.56

MPC

0.96

ClinPred

0.85

GERP RS

4.0

Varity_R

0.34

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over