Variant 7-151081596-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136044.2(TMUB1):c.694T>C(p.Phe232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,456,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

TMUB1
NM_001136044.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06100872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMUB1	NM_001136044.2 linkuse as main transcript	c.694T>C	p.Phe232Leu	missense_variant	3/3	ENST00000297533.9	NP_001129516.1	Q9BVT8A0A090N8Q3
TMUB1	NM_031434.4 linkuse as main transcript	c.694T>C	p.Phe232Leu	missense_variant	3/3		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.694T>C	p.Phe232Leu	missense_variant	3/3	1	NM_001136044.2	ENSP00000297533.4		Q9BVT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000340

AC:

AN:

235634

Hom.:

AF XY:

0.0000464

AC XY:

AN XY:

129230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000237

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1456736

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724280

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000226

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000167

AC:

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

Sep 16, 2021

The c.694T>C (p.F232L) alteration is located in exon 3 (coding exon 2) of the TMUB1 gene. This alteration results from a T to C substitution at nucleotide position 694, causing the phenylalanine (F) at amino acid position 232 to be replaced by a leucine (L). 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

0.73

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0047

T;T;T;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.64

.;.;.;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.061

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

N;N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.0

N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.21

T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.10

MutPred

0.36

Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);Gain of sheet (P = 0.0073);

MVP

0.20

MPC

0.96

ClinPred

0.15

GERP RS

2.8

Varity_R

0.050

gMVP

0.65

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

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