chr13-77055704-C-T

Variant names:

• chr13-77055704-C-T
• rs748308347
• NM_015057.5:c.13501G>A

Variant summary

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

The NM_015057.5(MYCBP2):​c.13501G>A​(p.Val4501Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,870 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V4501F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: MYCBP2 NM_015057.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

Genes affected

MYCBP2 (HGNC:23386): (MYC binding protein 2) This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect. [provided by RefSeq, Mar 2017]

ENSG00000283208 (HGNC:):

MYCBP2-AS1 (HGNC:41023): (MYCBP2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13887519).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015057.5. 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
	MYCBP2	NM_015057.5	MANE Select	c.13501G>A	p.Val4501Ile	missense	Exon 80 of 83	NP_055872.4	O75592-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCBP2	ENST00000544440.7	TSL:1 MANE Select	c.13501G>A	p.Val4501Ile	missense	Exon 80 of 83	ENSP00000444596.2	O75592-1
	MYCBP2	ENST00000357337.11	TSL:1	c.13681G>A	p.Val4561Ile	missense	Exon 81 of 84	ENSP00000349892.6	A0A499FJI4
	ENSG00000283208	ENST00000638147.2	TSL:5	c.566-19814C>T		intron	N/A	ENSP00000490953.2	A0A1B0GWJ7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000799 AC: 20 AN: 250374 AF XY: 0.0000443

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000579

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: 0.0000157 AC: 23 AN: 1461654 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000492 AC: 22 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.000131 AC: 2 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

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

Alfa AF: 0.0000261 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.035
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		7.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.10
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.023	D
Vest4		0.55
MutPred		0.26		Gain of catalytic residue at L4468 (P = 0)
MVP		0.32
MPC		1.6
ClinPred		0.25	T
GERP RS		4.2
Mutation Taster		=76/24	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: rs748308347; hg19: chr13-77629839;