17-4539815-G-T

Variant names:

• chr17-4539815-G-T
• NM_014520.4:c.3587C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_014520.4(MYBBP1A):​c.3587C>A​(p.Thr1196Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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.

• PM1: In a modified_residue Phosphothreonine (size 0) in uniprot entity MBB1A_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03604114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBBP1A	NM_014520.4	c.3587C>A	p.Thr1196Lys	missense_variant	Exon 26 of 26	ENST00000254718.9	NP_055335.2
MYBBP1A	NM_001105538.2	c.3587C>A	p.Thr1196Lys	missense_variant	Exon 26 of 27		NP_001099008.1
MYBBP1A	XM_011523616.3	c.2831C>A	p.Thr944Lys	missense_variant	Exon 21 of 21		XP_011521918.1
MYBBP1A	XM_024450536.2	c.*87C>A		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.3587C>A	p.Thr1196Lys	missense_variant	Exon 26 of 26	1	NM_014520.4	ENSP00000254718.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459278 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726096

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.018
DANN	Benign	0.75
DEOGEN2	Benign	0.026	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.035
Sift	Benign	0.53	T;T
Sift4G	Benign	0.95	T;T
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.25		Loss of phosphorylation at T1196 (P = 0.0013);Loss of phosphorylation at T1196 (P = 0.0013);
MVP		0.41
ClinPred		0.025	T
GERP RS		-0.81
Varity_R		0.035
gMVP		0.053

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: chr17-4443110;