Variant 19-17420625-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001304547.2(MVB12A):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MVB12A
NM_001304547.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

MVB12A (HGNC:25153): (multivesicular body subunit 12A) Enables lipid binding activity and ubiquitin binding activity. Involved in regulation of epidermal growth factor receptor signaling pathway; viral budding; and virus maturation. Located in several cellular components, including Golgi apparatus; centrosome; and nucleoplasm. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

MVB12A links:

ENSG00000269481 (HGNC:):

ENSG00000269481 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 13 codons. Genomic position: 17422358. Lost 0.068 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MVB12A	NM_138401.4 link	c.277A>G	p.Met93Val	missense_variant	Exon 3 of 9	ENST00000317040.12	NP_612410.1	Q96EY5-1A0A024R7L6
MVB12A	NM_001304547.2 link	c.1A>G	p.Met1?	start_lost	Exon 4 of 10		NP_001291476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MVB12A	ENST00000317040.12 link	c.277A>G	p.Met93Val	missense_variant	Exon 3 of 9	1	NM_138401.4	ENSP00000324810.6		Q96EY5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1457276

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725318

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.277A>G (p.M93V) alteration is located in exon 3 (coding exon 3) of the MVB12A gene. This alteration results from a A to G substitution at nucleotide position 277, causing the methionine (M) at amino acid position 93 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0091

T;T;T;T;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.90

.;D;.;T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;N;.;.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.47

N;.;N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.28

T;.;T;T;T;T

Sift4G

Benign

0.16

T;T;T;T;T;T

Polyphen

0.0010

.;.;B;.;.;B

Vest4

0.12, 0.11, 0.15

MutPred

0.31

.;.;Loss of catalytic residue at V89 (P = 0.0208);Loss of catalytic residue at V89 (P = 0.0208);Loss of catalytic residue at V89 (P = 0.0208);Loss of catalytic residue at V89 (P = 0.0208);

MVP

0.25

MPC

0.19

ClinPred

0.090

GERP RS

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over