17-4539683-C-G

Position:

• chr17-4539683-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014520.4(MYBBP1A):​c.3719G>C​(p.Arg1240Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1240W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.12

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04458815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBBP1A	NM_014520.4	c.3719G>C	p.Arg1240Pro	missense_variant	26/26	ENST00000254718.9
MYBBP1A	NM_001105538.2	c.3719G>C	p.Arg1240Pro	missense_variant	26/27
MYBBP1A	XM_011523616.3	c.2963G>C	p.Arg988Pro	missense_variant	21/21
MYBBP1A	XM_024450536.2	c.*219G>C		3_prime_UTR_variant	25/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3719G>C	p.Arg1240Pro	missense_variant	26/26	1	NM_014520.4	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.3719G>C (p.R1240P) alteration is located in exon 26 (coding exon 26) of the MYBBP1A gene. This alteration results from a G to C substitution at nucleotide position 3719, causing the arginine (R) at amino acid position 1240 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.1
DANN	Benign	0.51
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.075
Sift	Benign	0.26	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.25		Loss of MoRF binding (P = 0.0032);Loss of MoRF binding (P = 0.0032);
MVP		0.37
ClinPred		0.25	T
GERP RS		0.50
Varity_R		0.14
gMVP		0.086

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4442978;