7-151082238-A-G

Variant names:

• chr7-151082238-A-G
• rs1008503443
• NM_001136044.2:c.326T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001136044.2(TMUB1):​c.326T>C​(p.Phe109Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,549,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. F109Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TMUB1 NM_001136044.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

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.326T>C	p.Phe109Ser	missense	Exon 2 of 3	NP_001129516.1	Q9BVT8
	TMUB1	NM_031434.4		c.326T>C	p.Phe109Ser	missense	Exon 2 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.326T>C	p.Phe109Ser	missense	Exon 2 of 3	ENSP00000297533.4	Q9BVT8
	TMUB1	ENST00000392818.7	TSL:1	c.326T>C	p.Phe109Ser	missense	Exon 2 of 3	ENSP00000376565.3	Q9BVT8
	TMUB1	ENST00000462940.1	TSL:1	c.326T>C	p.Phe109Ser	missense	Exon 1 of 2	ENSP00000417519.1	Q9BVT8

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000186 AC: 26 AN: 1397044 Hom.: 0 Cov.: 31 AF XY: 0.0000218 AC XY: 15 AN XY: 689304

African (AFR) AF: 0.00 AC: 0 AN: 31160

American (AMR) AF: 0.00 AC: 0 AN: 34960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21850

East Asian (EAS) AF: 0.00 AC: 0 AN: 38270

South Asian (SAS) AF: 0.00 AC: 0 AN: 76800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51460

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5468

European-Non Finnish (NFE) AF: 0.0000232 AC: 25 AN: 1079504

Other (OTH) AF: 0.00 AC: 0 AN: 57572

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152052 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.60		Gain of disorder (P = 0.0133)
MVP		0.81
MPC		1.2
ClinPred		1.0	D
GERP RS		4.0
PromoterAI		-0.020	Neutral
Varity_R		0.91
gMVP		0.77
Mutation Taster		=58/42	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: rs1008503443; hg19: chr7-150779325;