7-151082188-C-T

Variant names:

• chr7-151082188-C-T
• rs1355911083
• NM_001136044.2:c.376G>A

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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]

ACMG classification

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
TMUB1	NM_001136044.2	c.376G>A	p.Gly126Ser	missense_variant	Exon 2 of 3	ENST00000297533.9	NP_001129516.1
TMUB1	NM_031434.4	c.376G>A	p.Gly126Ser	missense_variant	Exon 2 of 3		NP_113622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMUB1	ENST00000297533.9	c.376G>A	p.Gly126Ser	missense_variant	Exon 2 of 3	1	NM_001136044.2	ENSP00000297533.4

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

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

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

Other links and lift over

dbSNP: rs1355911083; hg19: chr7-150779275;