rs755560565

Variant names:

• chr17-4539769-C-G
• rs755560565
• NM_014520.4:c.3633G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-4539769-C-G
• chr17-4539769-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014520.4(MYBBP1A):​c.3633G>C​(p.Lys1211Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MYBBP1A NM_014520.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.960
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14772329).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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.3633G>C	p.Lys1211Asn	missense	Exon 26 of 26	NP_055335.2	Q9BQG0-1
	MYBBP1A	NM_001105538.2		c.3633G>C	p.Lys1211Asn	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.3633G>C	p.Lys1211Asn	missense	Exon 26 of 26	ENSP00000254718.4	Q9BQG0-1
	MYBBP1A	ENST00000573116.5	TSL:1	c.3390G>C	p.Lys1130Asn	missense	Exon 25 of 26	ENSP00000458919.1	I3L1L3
	MYBBP1A	ENST00000574547.5	TSL:1	n.1201G>C		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250760 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

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: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1460806 Hom.: 0 Cov.: 36 AF XY: 0.0000124 AC XY: 9 AN XY: 726780

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52364

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111988

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152158 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.96
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.42	B
Vest4		0.33
MutPred		0.22		Loss of methylation at K1211 (P = 0.0067)
MVP		0.63
ClinPred		0.79	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.13
gMVP		0.043
Mutation Taster		=77/23	polymorphism

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: rs755560565; hg19: chr17-4443064;