13-77061194-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_015057.5(MYCBP2):ā€‹c.13011A>Gā€‹(p.Ala4337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,608,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.00023 ( 0 hom., cov: 32)
Exomes š‘“: 0.00041 ( 1 hom. )

Consequence

MYCBP2
NM_015057.5 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.169
Variant links:
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]
MYCBP2-AS1 (HGNC:41023): (MYCBP2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 13-77061194-T-C is Benign according to our data. Variant chr13-77061194-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055363.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.169 with no splicing effect.
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYCBP2NM_015057.5 linkuse as main transcriptc.13011A>G p.Ala4337= synonymous_variant 76/83 ENST00000544440.7 NP_055872.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYCBP2ENST00000544440.7 linkuse as main transcriptc.13011A>G p.Ala4337= synonymous_variant 76/831 NM_015057.5 ENSP00000444596 A1O75592-1

Frequencies

GnomAD3 genomes
AF:
0.000237
AC:
36
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000399
AC:
98
AN:
245882
Hom.:
0
AF XY:
0.000474
AC XY:
63
AN XY:
133050
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000181
Gnomad ASJ exome
AF:
0.000703
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000101
Gnomad FIN exome
AF:
0.0000927
Gnomad NFE exome
AF:
0.000688
Gnomad OTH exome
AF:
0.000503
GnomAD4 exome
AF:
0.000406
AC:
592
AN:
1456446
Hom.:
1
Cov.:
31
AF XY:
0.000399
AC XY:
289
AN XY:
724456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000182
Gnomad4 ASJ exome
AF:
0.000808
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000200
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.000455
Gnomad4 OTH exome
AF:
0.000466
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000442
Hom.:
0
Bravo
AF:
0.000230
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MYCBP2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 28, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
5.5
DANN
Benign
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146032966; hg19: chr13-77635329; API