chr17-4555186-G-T

Position:

• chr17-4555186-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014520.4(MYBBP1A):​c.139C>A​(p.Gln47Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,252 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.139C>A	p.Gln47Lys	missense_variant	1/26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.139C>A	p.Gln47Lys	missense_variant	1/27		NP_001099008.1
MYBBP1A	XM_024450536.2	c.139C>A	p.Gln47Lys	missense_variant	1/25		XP_024306304.1
MYBBP1A	XM_047435119.1	c.139C>A	p.Gln47Lys	missense_variant	1/17		XP_047291075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.139C>A	p.Gln47Lys	missense_variant	1/26	1	NM_014520.4	ENSP00000254718.4
MYBBP1A	ENST00000381556.6	c.139C>A	p.Gln47Lys	missense_variant	1/27	5		ENSP00000370968.2
MYBBP1A	ENST00000570986.1	n.173C>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74386

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.71	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.25
Sift	Benign	0.19	T;T
Sift4G	Uncertain	0.033	D;D
Polyphen		0.98	D;D
Vest4		0.43
MutPred		0.43		Gain of ubiquitination at Q47 (P = 0.0104);Gain of ubiquitination at Q47 (P = 0.0104);
MVP		0.85
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs758083465; hg19: chr17-4458481;