chr17-4539639-T-C

Position:

• chr17-4539639-T-C

Variant summary

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

The NM_014520.4(MYBBP1A):​c.3763A>G​(p.Asn1255Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

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 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=0.040623903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.3763A>G	p.Asn1255Asp	missense_variant	26/26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.3763A>G	p.Asn1255Asp	missense_variant	26/27		NP_001099008.1
MYBBP1A	XM_011523616.3	c.3007A>G	p.Asn1003Asp	missense_variant	21/21		XP_011521918.1
MYBBP1A	XM_024450536.2	c.*263A>G		3_prime_UTR_variant	25/25		XP_024306304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3763A>G	p.Asn1255Asp	missense_variant	26/26	1	NM_014520.4	ENSP00000254718.4

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

Dec 10, 2024

The c.3763A>G (p.N1255D) alteration is located in exon 26 (coding exon 26) of the MYBBP1A gene. This alteration results from a A to G substitution at nucleotide position 3763, causing the asparagine (N) at amino acid position 1255 to be replaced by an aspartic acid (D). 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	0.092
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.7
DANN	Benign	0.55
DEOGEN2	Benign	0.046	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.90	N;N
REVEL	Benign	0.022
Sift	Benign	0.43	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0060	B;B
Vest4		0.16
MutPred		0.18		Loss of MoRF binding (P = 0.0565);Loss of MoRF binding (P = 0.0565);
MVP		0.44
ClinPred		0.088	T
GERP RS		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.014

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: chr17-4442934;