17-4539613-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014520.4(MYBBP1A):c.3789A>T(p.Gly1263=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.648

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]

ACMG classification

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 GnomAd at 240 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBBP1A	NM_014520.4	c.3789A>T	p.Gly1263=	synonymous_variant	26/26	ENST00000254718.9
MYBBP1A	NM_001105538.2	c.3789A>T	p.Gly1263=	synonymous_variant	26/27
MYBBP1A	XM_011523616.3	c.3033A>T	p.Gly1011=	synonymous_variant	21/21
MYBBP1A	XM_024450536.2	c.*289A>T		3_prime_UTR_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3789A>T	p.Gly1263=	synonymous_variant	26/26	1	NM_014520.4	P2

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152002 Hom.: 2 Cov.: 31

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.: 1 AF XY: 0.00136 AC XY: 185 AN XY: 135872

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.: 3 Cov.: 37 AF XY: 0.00168 AC XY: 1224 AN XY: 727204

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.: 2 Cov.: 31 AF XY: 0.00172 AC XY: 128 AN XY: 74376

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.: 0

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

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

Other links and lift over

dbSNP: rs150145302; hg19: chr17-4442908;