rs1414629008

Variant names:

• chr7-151081769-C-A
• 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. Variant got 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. 14/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMUB1	NM_001136044.2	c.521G>T	p.Arg174Ile	missense_variant	Exon 3 of 3	ENST00000297533.9	NP_001129516.1
TMUB1	NM_031434.4	c.521G>T	p.Arg174Ile	missense_variant	Exon 3 of 3		NP_113622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMUB1	ENST00000297533.9	c.521G>T	p.Arg174Ile	missense_variant	Exon 3 of 3	1	NM_001136044.2	ENSP00000297533.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000244

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T;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;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.97	D;D;D;D;D
Vest4		0.34
MutPred		0.25		Loss of solvent accessibility (P = 0.0249);Loss of solvent accessibility (P = 0.0249);Loss of solvent accessibility (P = 0.0249);Loss of solvent accessibility (P = 0.0249);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150778856;