8-143816981-G-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_078480.3(PUF60):c.1309C>T(p.Gln437*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PUF60
NM_078480.3 stop_gained
NM_078480.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.29
Publications
0 publications found
Genes affected
PUF60 (HGNC:17042): (poly(U) binding splicing factor 60) This gene encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. The encoded protein forms a complex with the far upstream DNA element (FUSE) and FUSE-binding protein at the myelocytomatosis oncogene (MYC) promoter. This complex represses MYC transcription through the core-TFIIH basal transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
PUF60 Gene-Disease associations (from GenCC):
- 8q24.3 microdeletion syndromeInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
- syndromic intellectual disabilityInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-143816981-G-A is Pathogenic according to our data. Variant chr8-143816981-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 545569.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1452182Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0AN XY: 721598
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1452182
Hom.:
Cov.:
38
AF XY:
AC XY:
0
AN XY:
721598
African (AFR)
AF:
AC:
0
AN:
33350
American (AMR)
AF:
AC:
0
AN:
43344
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25948
East Asian (EAS)
AF:
AC:
0
AN:
39308
South Asian (SAS)
AF:
AC:
0
AN:
84904
European-Finnish (FIN)
AF:
AC:
0
AN:
51800
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1107766
Other (OTH)
AF:
AC:
0
AN:
60004
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
8q24.3 microdeletion syndrome Pathogenic:1
Mar 27, 2018
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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