rs1414629008

Variant names:

• chr7-151081769-C-A
• rs1414629008
• NM_001136044.2:c.521G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151081769-C-A
• chr7-151081769-C-G
• chr7-151081769-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136044.2(TMUB1):​c.521G>T​(p.Arg174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R174K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMUB1 NM_001136044.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18728068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136044.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMUB1	NM_001136044.2	MANE Select	c.521G>T	p.Arg174Ile	missense	Exon 3 of 3	NP_001129516.1	Q9BVT8
	TMUB1	NM_031434.4		c.521G>T	p.Arg174Ile	missense	Exon 3 of 3	NP_113622.1	Q9BVT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMUB1	ENST00000297533.9	TSL:1 MANE Select	c.521G>T	p.Arg174Ile	missense	Exon 3 of 3	ENSP00000297533.4	Q9BVT8
	TMUB1	ENST00000392818.7	TSL:1	c.521G>T	p.Arg174Ile	missense	Exon 3 of 3	ENSP00000376565.3	Q9BVT8
	TMUB1	ENST00000462940.1	TSL:1	c.521G>T	p.Arg174Ile	missense	Exon 2 of 2	ENSP00000417519.1	Q9BVT8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442874 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 715584

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.0000244 AC: 1 AN: 41062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.00 AC: 0 AN: 39050

South Asian (SAS) AF: 0.00 AC: 0 AN: 83208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104146

Other (OTH) AF: 0.00 AC: 0 AN: 59820

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.085
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Benign	0.20	T
Sift4G	Benign	0.10	T
Polyphen		0.97	D
Vest4		0.34
MutPred		0.25		Loss of solvent accessibility (P = 0.0249)
MVP		0.49
MPC		1.3
ClinPred		0.61	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.49
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1414629008; hg19: chr7-150778856;