17-4555186-G-C

Position:

• chr17-4555186-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014520.4(MYBBP1A):​c.139C>G​(p.Gln47Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33204496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBBP1A	NM_014520.4	c.139C>G	p.Gln47Glu	missense_variant	1/26	ENST00000254718.9
MYBBP1A	NM_001105538.2	c.139C>G	p.Gln47Glu	missense_variant	1/27
MYBBP1A	XM_024450536.2	c.139C>G	p.Gln47Glu	missense_variant	1/25
MYBBP1A	XM_047435119.1	c.139C>G	p.Gln47Glu	missense_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.139C>G	p.Gln47Glu	missense_variant	1/26	1	NM_014520.4	P2
MYBBP1A	ENST00000381556.6	c.139C>G	p.Gln47Glu	missense_variant	1/27	5		A2
MYBBP1A	ENST00000570986.1	n.173C>G		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000420 AC: 1 AN: 238074 Hom.: 0 AF XY: 0.00000772 AC XY: 1 AN XY: 129536

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455586 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	0.98
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.54	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.80	N;N
REVEL	Benign	0.14
Sift	Benign	0.30	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.80	P;P
Vest4		0.43
MutPred		0.34		Gain of disorder (P = 0.0655);Gain of disorder (P = 0.0655);
MVP		0.83
ClinPred		0.45	T
GERP RS		4.8
Varity_R		0.27
gMVP		0.17

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;