Variant 9-126326965-CCCG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_033446.3(MVB12B):c.47_49delCGC(p.Pro16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 261,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0038 ( 0 hom. )

Consequence

MVB12B
NM_033446.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.40

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 9-126326965-CCCG-C is Benign according to our data. Variant chr9-126326965-CCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3042318.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MVB12B	NM_033446.3 link	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	1/10	ENST00000361171.8	NP_258257.1	Q9H7P6-1A0A024R8B8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MVB12B	ENST00000361171.8 link	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	1/10	2	NM_033446.3	ENSP00000354772.3		Q9H7P6-1
MVB12B	ENST00000489637.3 link	c.47_49delCGC	p.Pro16del	disruptive_inframe_deletion	1/6	1		ENSP00000485994.1		Q9H7P6-2

Frequencies

GnomAD3 genomes

AF:

0.0000208

AC:

AN:

143956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000366

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00217

AC:

AN:

36018

Hom.:

AF XY:

0.00217

AC XY:

AN XY:

21646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00294

Gnomad SAS exome

AF:

0.00204

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.000940

GnomAD4 exome

AF:

0.00376

AC:

442

AN:

117592

Hom.:

AF XY:

0.00365

AC XY:

273

AN XY:

74768

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.000953

Gnomad4 SAS exome

AF:

0.00428

Gnomad4 FIN exome

AF:

0.00545

Gnomad4 NFE exome

AF:

0.00367

Gnomad4 OTH exome

AF:

0.00483

GnomAD4 genome

AF:

0.0000208

AC:

AN:

144056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70118

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000366

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MVB12B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2022

This variant is classified as likely 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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