9-126422030-G-C

Variant names:

• chr9-126422030-G-C
• rs887659
• NM_033446.3:c.757+82G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033446.3(MVB12B):​c.757+82G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MVB12B NM_033446.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	NM_033446.3	MANE Select	c.757+82G>C		intron	N/A	NP_258257.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.757+82G>C		intron	N/A	ENSP00000354772.3
	MVB12B	ENST00000470567.5	TSL:5	n.153+82G>C		intron	N/A
	MVB12B	ENST00000489570.1	TSL:3	n.95+82G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 832600 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 437476

African (AFR) AF: 0.00 AC: 0 AN: 21584

American (AMR) AF: 0.00 AC: 0 AN: 42026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21798

East Asian (EAS) AF: 0.00 AC: 0 AN: 36560

South Asian (SAS) AF: 0.00 AC: 0 AN: 73018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 550864

Other (OTH) AF: 0.00 AC: 0 AN: 40228

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 66724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.011
DANN	Benign	0.55
PhyloP100		-1.2

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: rs887659; hg19: chr9-129184309;