NM_033446.3:c.135G>A

Variant names:

• chr9-126340561-G-A
• rs1888156
• NM_033446.3:c.135G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.969
• Publications: 18 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: Benign. The variant received -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 VariationId 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.

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.135G>A	p.Thr45Thr	synonymous	Exon 2 of 10	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.135G>A	p.Thr45Thr	synonymous	Exon 2 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.135G>A	p.Thr45Thr	synonymous	Exon 2 of 10	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000489637.3	TSL:1	c.135G>A	p.Thr45Thr	synonymous	Exon 2 of 6	ENSP00000485994.1	Q9H7P6-2
	MVB12B	ENST00000885963.1		c.135G>A	p.Thr45Thr	synonymous	Exon 2 of 11	ENSP00000556022.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50094 AN: 151984 Hom.: 8353 Cov.: 33

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

GnomAD2 exomes AF: 0.323 AC: 81233 AN: 251450 AF XY: 0.319

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 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.: 34 AF XY: 0.318 AC XY: 231052 AN XY: 727012

African (AFR) AF: 0.365 AC: 12211 AN: 33472

American (AMR) AF: 0.337 AC: 15068 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 7079 AN: 26128

East Asian (EAS) AF: 0.274 AC: 10889 AN: 39690

South Asian (SAS) AF: 0.288 AC: 24855 AN: 86228

European-Finnish (FIN) AF: 0.396 AC: 21144 AN: 53406

Middle Eastern (MID) AF: 0.258 AC: 1486 AN: 5762

European-Non Finnish (NFE) AF: 0.320 AC: 355593 AN: 1111640

Other (OTH) AF: 0.308 AC: 18589 AN: 60376

GnomAD4 genome AF: 0.329 AC: 50116 AN: 152102 Hom.: 8357 Cov.: 33 AF XY: 0.331 AC XY: 24614 AN XY: 74332

African (AFR) AF: 0.364 AC: 15089 AN: 41482

American (AMR) AF: 0.290 AC: 4435 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1452 AN: 5186

South Asian (SAS) AF: 0.301 AC: 1446 AN: 4808

European-Finnish (FIN) AF: 0.395 AC: 4162 AN: 10548

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21745 AN: 67994

Other (OTH) AF: 0.307 AC: 650 AN: 2114

Alfa AF: 0.315 Hom.: 15767

Bravo AF: 0.326

Asia WGS AF: 0.302 AC: 1050 AN: 3478

EpiCase AF: 0.298

EpiControl AF: 0.297

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MVB12B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	6.1
DANN	Benign	0.85
PhyloP100		0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1888156; hg19: chr9-129102840; COSMIC: COSV63257354;