NM_033446.3:c.388A>G

Variant names:

• chr9-126386637-A-G
• rs142076731
• NM_033446.3:c.388A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033446.3(MVB12B):​c.388A>G​(p.Ile130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: MVB12B NM_033446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15067697).

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.388A>G	p.Ile130Val	missense	Exon 4 of 10	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.388A>G	p.Ile130Val	missense	Exon 4 of 6	NP_001011703.1	Q9H7P6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MVB12B	ENST00000361171.8	TSL:2 MANE Select	c.388A>G	p.Ile130Val	missense	Exon 4 of 10	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000489637.3	TSL:1	c.388A>G	p.Ile130Val	missense	Exon 4 of 6	ENSP00000485994.1	Q9H7P6-2
	MVB12B	ENST00000885963.1		c.388A>G	p.Ile130Val	missense	Exon 4 of 11	ENSP00000556022.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251404 AF XY: 0.0000515

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1461438 Hom.: 0 Cov.: 29 AF XY: 0.0000385 AC XY: 28 AN XY: 727072

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111630

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74480

African (AFR) AF: 0.0000241 AC: 1 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000186 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.095	N
PhyloP100		3.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.15
Sift	Benign	0.33	T
Sift4G	Benign	0.56	T
Polyphen		0.45	B
Vest4		0.099
MVP		0.10
MPC		0.50
ClinPred		0.076	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.21
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs142076731; hg19: chr9-129148916;