7-151082188-C-T

Variant summary

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

The NM_001136044.2(TMUB1):​c.376G>A​(p.Gly126Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000221 in 1,359,472 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: 0.0000022 ( 0 hom. )

Consequence

TMUB1
NM_001136044.2 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83
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]

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 rank MANE Protein UniProt
TMUB1NM_001136044.2 linkc.376G>A p.Gly126Ser missense_variant Exon 2 of 3 ENST00000297533.9 NP_001129516.1 Q9BVT8A0A090N8Q3
TMUB1NM_031434.4 linkc.376G>A p.Gly126Ser missense_variant Exon 2 of 3 NP_113622.1 Q9BVT8A0A090N8Q3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMUB1ENST00000297533.9 linkc.376G>A p.Gly126Ser missense_variant Exon 2 of 3 1 NM_001136044.2 ENSP00000297533.4 Q9BVT8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000221
AC:
3
AN:
1359472
Hom.:
0
Cov.:
31
AF XY:
0.00000301
AC XY:
2
AN XY:
665162
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:
0.00000283
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.376G>A (p.G126S) alteration is located in exon 2 (coding exon 1) of the TMUB1 gene. This alteration results from a G to A substitution at nucleotide position 376, causing the glycine (G) at amino acid position 126 to be replaced by a serine (S). 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
0.30
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T;T;T;T;T;.
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.85
.;.;.;.;D;D;D
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.58
D;D;D;D;D;D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.9
M;M;M;M;M;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-4.8
D;D;D;D;D;D;D
REVEL
Benign
0.26
Sift
Benign
0.12
T;T;T;T;T;D;D
Sift4G
Uncertain
0.054
T;T;T;T;T;.;T
Polyphen
0.99
D;D;D;D;D;.;.
Vest4
0.77
MutPred
0.35
Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);Gain of disorder (P = 0.079);
MVP
0.54
MPC
0.89
ClinPred
1.0
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.66
gMVP
0.66

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.

Other links and lift over

dbSNP: rs1355911083; hg19: chr7-150779275; API