Genetic Variant MYBBP1A:p.Gln47* (chr17-4555186-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014520.4(MYBBP1A):c.139C>T(p.Gln47*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000311 in 1,607,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MYBBP1A
NM_014520.4 stop_gained

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

MYBBP1A (HGNC:7546): (MYB binding protein 1a) This gene encodes a nucleolar transcriptional regulator that was first identified by its ability to bind specifically to the Myb proto-oncogene protein. The encoded protein is thought to play a role in many cellular processes including response to nucleolar stress, tumor suppression and synthesis of ribosomal DNA. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MYBBP1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 26	ENST00000254718.9	NP_055335.2	Q9BQG0-1
MYBBP1A	NM_001105538.2 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 27		NP_001099008.1	Q9BQG0-2
MYBBP1A	XM_024450536.2 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 25		XP_024306304.1
MYBBP1A	XM_047435119.1 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 17		XP_047291075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYBBP1A	ENST00000254718.9 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 26	1	NM_014520.4	ENSP00000254718.4	Q9BQG0-1
MYBBP1A	ENST00000381556.6 link	c.139C>T	p.Gln47*	stop_gained	Exon 1 of 27	5		ENSP00000370968.2	Q9BQG0-2
MYBBP1A	ENST00000570986.1 link	n.173C>T		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000840

AC:

AN:

238074

AF XY:

0.0000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455586

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33418

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44008

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25930

Gnomad4 EAS exome

AF:

0.0000253

AC:

AN:

39538

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

85370

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51998

Gnomad4 NFE exome

AF:

0.00000180

AC:

AN:

1109430

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

60134

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.0000654

AC:

0.0000654279

AN:

0.0000654279

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000384

Hom.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autism

Uncertain:1

Jul 05, 2015

Lyon Laboratory, Cold Spring Harbor Laboratory

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.95

Vest4

0.70

GERP RS

4.8

Mutation Taster

=7/193

disease causing (fs/PTC)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over