17-4539629-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014520.4(MYBBP1A):c.3773C>T(p.Pro1258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010748297).
• BP6: Variant 17-4539629-G-A is Benign according to our data. Variant chr17-4539629-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2374861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBBP1A	NM_014520.4	c.3773C>T	p.Pro1258Leu	missense_variant	26/26	ENST00000254718.9
MYBBP1A	NM_001105538.2	c.3773C>T	p.Pro1258Leu	missense_variant	26/27
MYBBP1A	XM_011523616.3	c.3017C>T	p.Pro1006Leu	missense_variant	21/21
MYBBP1A	XM_024450536.2	c.*273C>T		3_prime_UTR_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3773C>T	p.Pro1258Leu	missense_variant	26/26	1	NM_014520.4	P2

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 20 AN: 152046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.0000716 AC: 18 AN: 251242 Hom.: 0 AF XY: 0.0000663 AC XY: 9 AN XY: 135786

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000589 AC: 86 AN: 1460992 Hom.: 0 Cov.: 36 AF XY: 0.0000674 AC XY: 49 AN XY: 726676

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0000896

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000132 AC: 20 AN: 152046 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 74272

Gnomad4 AFR AF: 0.000266

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000480

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.035
Dann	Benign	0.76
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.60	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.35	N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;B
Vest4		0.15
MVP		0.46
ClinPred		0.0063	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.022

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: rs778149572; hg19: chr17-4442924; COSMIC: COSV54604119; COSMIC: COSV54604119;