Variant rs2236786 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001127266.2(TMEM129):c.789A>G(p.Thr263Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,548,846 control chromosomes in the GnomAD database, including 29,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2440 hom., cov: 34)

Exomes 𝑓: 0.19 ( 27441 hom. )

Consequence

TMEM129
NM_001127266.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.22

Variant links:

Genes affected

TMEM129 (HGNC:25137): (transmembrane protein 129, E3 ubiquitin ligase) Enables ubiquitin protein ligase activity. Involved in protein polyubiquitination; retrograde protein transport, ER to cytosol; and ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMEM129 links:

TACC3 (HGNC:11524): (transforming acidic coiled-coil containing protein 3) This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells. [provided by RefSeq, Nov 2011]

TACC3 links:

TMEM129 (HGNC:):

TMEM129 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-4.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM129	NM_001127266.2 linkuse as main transcript	c.789A>G	p.Thr263Thr	synonymous_variant	3/4	ENST00000382936.8	NP_001120738.1	A0AVI4-1
TMEM129	NM_138385.4 linkuse as main transcript	c.681-139A>G		intron_variant			NP_612394.1	A0AVI4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM129	ENST00000382936.8 linkuse as main transcript	c.789A>G	p.Thr263Thr	synonymous_variant	3/4	1	NM_001127266.2	ENSP00000372394.3		A0AVI4-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24318

AN:

152084

Hom.:

2440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.210

AC:

31671

AN:

150554

Hom.:

3628

AF XY:

0.209

AC XY:

16690

AN XY:

79916

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.195

AC:

271707

AN:

1396644

Hom.:

27441

Cov.:

AF XY:

0.195

AC XY:

134453

AN XY:

688682

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.160

AC:

24309

AN:

152202

Hom.:

2440

Cov.:

AF XY:

0.165

AC XY:

12295

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0387

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.177

Hom.:

2297

Bravo

AF:

0.156

Asia WGS

AF:

0.162

AC:

560

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over