Genetic Variant MYBBP1A:p.Gly1263Gly (chr17-4539613-T-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014520.4(MYBBP1A):c.3789A>T(p.Gly1263Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,942 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

MYBBP1A
NM_014520.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.648

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-4539613-T-A is Benign according to our data. Variant chr17-4539613-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647260.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.648 with no splicing effect.

BS2

High AC in GnomAd4 at 240 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4 link	c.3789A>T	p.Gly1263Gly	synonymous_variant	Exon 26 of 26	ENST00000254718.9	NP_055335.2	Q9BQG0-1
MYBBP1A	NM_001105538.2 link	c.3789A>T	p.Gly1263Gly	synonymous_variant	Exon 26 of 27		NP_001099008.1	Q9BQG0-2
MYBBP1A	XM_011523616.3 link	c.3033A>T	p.Gly1011Gly	synonymous_variant	Exon 21 of 21		XP_011521918.1
MYBBP1A	XM_024450536.2 link	c.*289A>T		3_prime_UTR_variant	Exon 25 of 25		XP_024306304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9 link	c.3789A>T	p.Gly1263Gly	synonymous_variant	Exon 26 of 26	1	NM_014520.4	ENSP00000254718.4		Q9BQG0-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00512

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.00193

GnomAD3 exomes

AF:

0.00132

AC:

333

AN:

251410

Hom.:

AF XY:

0.00136

AC XY:

185

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00172

AC:

2520

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1224

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152120

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00511

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00162

EpiCase

AF:

0.00278

EpiControl

AF:

0.00302

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYBBP1A: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.88

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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