chr17-44189396-T-G

Variant names:

• chr17-44189396-T-G
• rs776182870
• NM_001076674.3:c.410T>G

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.410T>G​(p.Leu137Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L137P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TMUB2 NM_001076674.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36
• 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=0.18418097).

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.410T>G	p.Leu137Arg	missense	Exon 3 of 4	NP_001070142.1	Q71RG4-1
	TMUB2	NM_001353177.2		c.410T>G	p.Leu137Arg	missense	Exon 3 of 4	NP_001340106.1	Q71RG4-1
	TMUB2	NM_001353181.2		c.410T>G	p.Leu137Arg	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.410T>G	p.Leu137Arg	missense	Exon 3 of 4	ENSP00000444565.1	Q71RG4-1
	TMUB2	ENST00000319511.6	TSL:1	c.350T>G	p.Leu117Arg	missense	Exon 2 of 3	ENSP00000313214.5	Q71RG4-2
	TMUB2	ENST00000357984.7	TSL:1	c.350T>G	p.Leu117Arg	missense	Exon 2 of 3	ENSP00000350672.3	Q71RG4-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250616 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461600 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8 AN XY: 727080

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

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111842

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.32		Gain of loop (P = 0.002)
MVP		0.75
MPC		0.12
ClinPred		0.30	T
GERP RS		5.2
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.33
gMVP		0.69

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: rs776182870; hg19: chr17-42266764;