Genetic Variant NM_033446.3:c.47_49dupCGC (chr9-126326965-C-CCCG) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_033446.3(MVB12B):c.47_49dupCGC(p.Pro16dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000053 in 264,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

MVB12B
NM_033446.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_033446.3

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033446.3. 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
	MVB12B	NM_033446.3	MANE Select	c.47_49dupCGC	p.Pro16dup	disruptive_inframe_insertion	Exon 1 of 10	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.47_49dupCGC	p.Pro16dup	disruptive_inframe_insertion	Exon 1 of 6	NP_001011703.1	Q9H7P6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.47_49dupCGC	p.Pro16dup	disruptive_inframe_insertion	Exon 1 of 10	ENSP00000354772.3	Q9H7P6-1
MVB12B	ENST00000489637.3	TSL:1	c.47_49dupCGC	p.Pro16dup	disruptive_inframe_insertion	Exon 1 of 6	ENSP00000485994.1	Q9H7P6-2
MVB12B	ENST00000885963.1		c.47_49dupCGC	p.Pro16dup	disruptive_inframe_insertion	Exon 1 of 11	ENSP00000556022.1

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

143960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000926

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000833

AC:

AN:

36018

AF XY:

0.0000462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000416

AC:

AN:

120234

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

76472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1854

American (AMR)

AF:

0.000250

AC:

AN:

7988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4648

East Asian (EAS)

AF:

0.00

AC:

AN:

2128

South Asian (SAS)

AF:

0.00

AC:

AN:

26262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

438

European-Non Finnish (NFE)

AF:

0.0000453

AC:

AN:

66216

Other (OTH)

AF:

0.00

AC:

AN:

5068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000625

AC:

AN:

143960

Hom.:

Cov.:

AF XY:

0.0000429

AC XY:

AN XY:

70008

show subpopulations

African (AFR)

AF:

0.0000249

AC:

AN:

40174

American (AMR)

AF:

0.000137

AC:

AN:

14612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00

AC:

AN:

4950

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000926

AC:

AN:

64798

Other (OTH)

AF:

0.00

AC:

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=74/26

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over