chr17-4539689-G-C

Variant names:

• chr17-4539689-G-C
• rs1409373704
• NM_014520.4:c.3713C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014520.4(MYBBP1A):​c.3713C>G​(p.Pro1238Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1238L) has been classified as Uncertain significance.

• 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: 0.463
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21124959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014520.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBBP1A	NM_014520.4	MANE Select	c.3713C>G	p.Pro1238Arg	missense	Exon 26 of 26	NP_055335.2	Q9BQG0-1
	MYBBP1A	NM_001105538.2		c.3713C>G	p.Pro1238Arg	missense	Exon 26 of 27	NP_001099008.1	Q9BQG0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBBP1A	ENST00000254718.9	TSL:1 MANE Select	c.3713C>G	p.Pro1238Arg	missense	Exon 26 of 26	ENSP00000254718.4	Q9BQG0-1
	MYBBP1A	ENST00000573116.5	TSL:1	c.3470C>G	p.Pro1157Arg	missense	Exon 25 of 26	ENSP00000458919.1	I3L1L3
	MYBBP1A	ENST00000574547.5	TSL:1	n.1281C>G		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249000 AF XY: 0.00000742

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 1456200 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 723634

African (AFR) AF: 0.0000303 AC: 1 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 44152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108216

Other (OTH) AF: 0.00 AC: 0 AN: 60096

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.46
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.067
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.010	D
Polyphen		0.96	D
Vest4		0.21
MutPred		0.36		Gain of MoRF binding (P = 0.0026)
MVP		0.57
ClinPred		0.55	D
GERP RS		2.4
Varity_R		0.044
gMVP		0.052

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

Other links and lift over

dbSNP: rs1409373704; hg19: chr17-4442984;