Variant 9-126340561-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_033446.3(MVB12B):c.135G>A(p.Thr45Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,613,512 control chromosomes in the GnomAD database, including 83,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 8357 hom., cov: 33)

Exomes 𝑓: 0.32 ( 75576 hom. )

Consequence

MVB12B
NM_033446.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.969

Variant links:

Genes affected

MVB12B (HGNC:23368): (multivesicular body subunit 12B) The protein encoded by this gene is a component of the ESCRT-I complex, a heterotetramer, which mediates the sorting of ubiquitinated cargo protein from the plasma membrane to the endosomal vesicle. ESCRT-I complex plays an essential role in HIV budding and endosomal protein sorting. Depletion and overexpression of this and related protein (MVB12A) inhibit HIV-1 infectivity and induce unusual viral assembly defects, indicating a role for MVB12 subunits in regulating ESCRT-mediated virus budding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MVB12B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-126340561-G-A is Benign according to our data. Variant chr9-126340561-G-A is described in ClinVar as [Benign]. Clinvar id is 3060638.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.969 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12B	NM_033446.3 link	c.135G>A	p.Thr45Thr	synonymous_variant	Exon 2 of 10	ENST00000361171.8	NP_258257.1	Q9H7P6-1A0A024R8B8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MVB12B	ENST00000361171.8 link	c.135G>A	p.Thr45Thr	synonymous_variant	Exon 2 of 10	2	NM_033446.3	ENSP00000354772.3	Q9H7P6-1
MVB12B	ENST00000489637.3 link	c.135G>A	p.Thr45Thr	synonymous_variant	Exon 2 of 6	1		ENSP00000485994.1	Q9H7P6-2
MVB12B	ENST00000402437.2 link	c.90G>A	p.Thr30Thr	synonymous_variant	Exon 2 of 6	3		ENSP00000384751.2	F8W922

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50094

AN:

151984

Hom.:

8353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.323

AC:

81233

AN:

251450

Hom.:

13482

AF XY:

0.319

AC XY:

43345

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.294

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.319

AC:

466914

AN:

1461410

Hom.:

75576

Cov.:

AF XY:

0.318

AC XY:

231052

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.288

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.329

AC:

50116

AN:

152102

Hom.:

8357

Cov.:

AF XY:

0.331

AC XY:

24614

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.280

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.313

Hom.:

12839

Bravo

AF:

0.326

Asia WGS

AF:

0.302

AC:

1050

AN:

3478

EpiCase

AF:

0.298

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MVB12B-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.1

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over