17-4539716-G-A

Variant names:

• chr17-4539716-G-A
• rs777465263
• NM_014520.4:c.3686C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014520.4(MYBBP1A):​c.3686C>T​(p.Thr1229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070085734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.3686C>T	p.Thr1229Ile	missense_variant	Exon 26 of 26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.3686C>T	p.Thr1229Ile	missense_variant	Exon 26 of 27		NP_001099008.1
MYBBP1A	XM_011523616.3	c.2930C>T	p.Thr977Ile	missense_variant	Exon 21 of 21		XP_011521918.1
MYBBP1A	XM_024450536.2	c.*186C>T		3_prime_UTR_variant	Exon 25 of 25		XP_024306304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBBP1A	ENST00000254718.9	c.3686C>T	p.Thr1229Ile	missense_variant	Exon 26 of 26	1	NM_014520.4	ENSP00000254718.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457702 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 724578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000178 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.069
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		0.0060	B;B
Vest4		0.19
MutPred		0.16		Loss of glycosylation at T1229 (P = 0.0096);Loss of glycosylation at T1229 (P = 0.0096);
MVP		0.38
ClinPred		0.083	T
GERP RS		0.50
Varity_R		0.046
gMVP		0.068

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: rs777465263; hg19: chr17-4443011;