17-44189216-C-G

Variant names:

• chr17-44189216-C-G
• rs369002221
• NM_001076674.3:c.230C>G

Variant summary

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

The NM_001076674.3(TMUB2):​c.230C>G​(p.Ser77Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S77Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMUB2 NM_001076674.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.230C>G	p.Ser77Cys	missense	Exon 3 of 4	NP_001070142.1	Q71RG4-1
	TMUB2	NM_001353177.2		c.230C>G	p.Ser77Cys	missense	Exon 3 of 4	NP_001340106.1	Q71RG4-1
	TMUB2	NM_001353181.2		c.230C>G	p.Ser77Cys	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.230C>G	p.Ser77Cys	missense	Exon 3 of 4	ENSP00000444565.1	Q71RG4-1
	TMUB2	ENST00000319511.6	TSL:1	c.170C>G	p.Ser57Cys	missense	Exon 2 of 3	ENSP00000313214.5	Q71RG4-2
	TMUB2	ENST00000357984.7	TSL:1	c.170C>G	p.Ser57Cys	missense	Exon 2 of 3	ENSP00000350672.3	Q71RG4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461488 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727038

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111758

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.40		Loss of disorder (P = 0.0294)
MVP		0.71
MPC		0.33
ClinPred		0.95	D
GERP RS		5.2
PromoterAI		-0.045	Neutral
Varity_R		0.23
gMVP		0.63

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: rs369002221; hg19: chr17-42266584;