17-44189276-C-T

Variant names:

• chr17-44189276-C-T
• rs369440160
• NM_001076674.3:c.290C>T

Variant summary

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

The NM_001076674.3(TMUB2):​c.290C>T​(p.Thr97Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,452,070 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. T97A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TMUB2 NM_001076674.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

Genes affected

TMUB2 (HGNC:28459): (transmembrane and ubiquitin like domain containing 2) Predicted to be involved in ubiquitin-dependent ERAD pathway. 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=0.08889231).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076674.3. 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
	TMUB2	NM_001076674.3	MANE Select	c.290C>T	p.Thr97Ile	missense	Exon 3 of 4	NP_001070142.1	Q71RG4-1
	TMUB2	NM_001353177.2		c.290C>T	p.Thr97Ile	missense	Exon 3 of 4	NP_001340106.1	Q71RG4-1
	TMUB2	NM_001353181.2		c.290C>T	p.Thr97Ile	missense	Exon 2 of 3	NP_001340110.1	Q71RG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMUB2	ENST00000538716.7	TSL:2 MANE Select	c.290C>T	p.Thr97Ile	missense	Exon 3 of 4	ENSP00000444565.1	Q71RG4-1
	TMUB2	ENST00000319511.6	TSL:1	c.230C>T	p.Thr77Ile	missense	Exon 2 of 3	ENSP00000313214.5	Q71RG4-2
	TMUB2	ENST00000357984.7	TSL:1	c.230C>T	p.Thr77Ile	missense	Exon 2 of 3	ENSP00000350672.3	Q71RG4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 241324 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452070 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 721460

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 84766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106394

Other (OTH) AF: 0.00 AC: 0 AN: 59984

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.048
Sift	Benign	0.049	D
Sift4G	Benign	0.17	T
Polyphen		0.037	B
Vest4		0.16
MutPred		0.26		Loss of glycosylation at T97 (P = 3e-04)
MVP		0.42
MPC		0.086
ClinPred		0.53	D
GERP RS		3.1
PromoterAI		0.0065	Neutral
Varity_R		0.10
gMVP		0.24

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: rs369440160; hg19: chr17-42266644;