Genetic Variant NM_138401.4:c.88G>C (chr19-17420223-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_138401.4(MVB12A):c.88G>C(p.Ala30Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,490,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MVB12A
NM_138401.4 missense, splice_region

Scores

Splicing: ADA: 0.8244

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29087546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138401.4. 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
	MVB12A	NM_138401.4	MANE Select	c.88G>C	p.Ala30Pro	missense splice_region	Exon 1 of 9	NP_612410.1	Q96EY5-1
	MVB12A	NM_001304547.2		c.-186-90G>C		intron	N/A	NP_001291476.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MVB12A	ENST00000317040.12	TSL:1 MANE Select	c.88G>C	p.Ala30Pro	missense splice_region	Exon 1 of 9	ENSP00000324810.6	Q96EY5-1
MVB12A	ENST00000529939.5	TSL:3	c.88G>C	p.Ala30Pro	missense splice_region	Exon 1 of 8	ENSP00000432526.1	E9PQA6
MVB12A	ENST00000875213.1		c.88G>C	p.Ala30Pro	missense splice_region	Exon 1 of 8	ENSP00000545272.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000760

AC:

AN:

131580

AF XY:

0.0000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1338514

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

655490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28724

American (AMR)

AF:

0.00

AC:

AN:

25344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19792

East Asian (EAS)

AF:

0.00

AC:

AN:

35940

South Asian (SAS)

AF:

0.00

AC:

AN:

67302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5026

European-Non Finnish (NFE)

AF:

0.0000293

AC:

AN:

1058572

Other (OTH)

AF:

0.0000181

AC:

AN:

55156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00000856

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0067

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.71

M_CAP

Benign

0.030

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.4

REVEL

Benign

0.24

Sift

Uncertain

0.021

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.32

MutPred

0.74

Gain of disorder (P = 0.1047)

MVP

0.72

MPC

0.79

ClinPred

0.40

GERP RS

4.9

PromoterAI

0.035

Neutral

(source)

Varity_R

0.62

gMVP

0.53

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.82

dbscSNV1_RF

Pathogenic

0.77

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over