NM_033446.3:c.297A>G

Variant names:

• chr9-126381156-A-G
• rs2286889
• NM_033446.3:c.297A>G

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.297A>G​(p.Ser99Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,612,318 control chromosomes in the GnomAD database, including 11,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.094 (913 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10247 hom.)
• Consequence: MVB12B NM_033446.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.471
• Publications: 14 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=-0.44).
• BP6: Variant 9-126381156-A-G is Benign according to our data. Variant chr9-126381156-A-G is described in ClinVar as Benign. ClinVar VariationId is 3061019.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.471 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 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.297A>G	p.Ser99Ser	synonymous	Exon 3 of 10	NP_258257.1	Q9H7P6-1
	MVB12B	NM_001011703.3		c.297A>G	p.Ser99Ser	synonymous	Exon 3 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.297A>G	p.Ser99Ser	synonymous	Exon 3 of 10	ENSP00000354772.3	Q9H7P6-1
	MVB12B	ENST00000489637.3	TSL:1	c.297A>G	p.Ser99Ser	synonymous	Exon 3 of 6	ENSP00000485994.1	Q9H7P6-2
	MVB12B	ENST00000885963.1		c.297A>G	p.Ser99Ser	synonymous	Exon 3 of 11	ENSP00000556022.1

Frequencies

GnomAD3 genomes AF: 0.0947 AC: 14400 AN: 152134 Hom.: 915 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.132 AC: 33130 AN: 251212 AF XY: 0.132

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.111 AC: 162188 AN: 1460066 Hom.: 10247 Cov.: 31 AF XY: 0.113 AC XY: 82012 AN XY: 726498

African (AFR) AF: 0.0168 AC: 561 AN: 33462

American (AMR) AF: 0.174 AC: 7786 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4471 AN: 26110

East Asian (EAS) AF: 0.249 AC: 9873 AN: 39684

South Asian (SAS) AF: 0.154 AC: 13242 AN: 86226

European-Finnish (FIN) AF: 0.114 AC: 6056 AN: 53272

Middle Eastern (MID) AF: 0.119 AC: 688 AN: 5762

European-Non Finnish (NFE) AF: 0.101 AC: 112271 AN: 1110506

Other (OTH) AF: 0.120 AC: 7240 AN: 60328

GnomAD4 genome AF: 0.0945 AC: 14387 AN: 152252 Hom.: 913 Cov.: 33 AF XY: 0.0974 AC XY: 7253 AN XY: 74444

African (AFR) AF: 0.0229 AC: 952 AN: 41570

American (AMR) AF: 0.121 AC: 1858 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1317 AN: 5168

South Asian (SAS) AF: 0.168 AC: 809 AN: 4828

European-Finnish (FIN) AF: 0.118 AC: 1246 AN: 10594

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7294 AN: 68000

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.107 Hom.: 1957

Bravo AF: 0.0936

Asia WGS AF: 0.204 AC: 708 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.108

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	-0.44
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		-0.47
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: rs2286889; hg19: chr9-129143435; COSMIC: COSV63257466;