16-68355785-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_019023.5(PRMT7):c.1713C>A(p.Cys571Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PRMT7
NM_019023.5 stop_gained
NM_019023.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 2.95
Genes affected
PRMT7 (HGNC:25557): (protein arginine methyltransferase 7) This gene encodes a member of the protein arginine N-methyltransferase family of proteins. The encoded enzyme transfers single methyl groups to arginine residues to generate monomethylarginines on histone proteins as well as other protein substrates. This enzyme plays a role in a wide range of biological processes, including neuronal differentiation, male germ line imprinting, small nuclear ribonucleoprotein biogenesis, and regulation of the Wnt signaling pathway. Mutations in this gene underlie multiple related syndromes in human patients characterized by intellectual disability, short stature and other features. The encoded protein may promote breast cancer cell invasion and metastasis in human patients. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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 16-68355785-C-A is Pathogenic according to our data. Variant chr16-68355785-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 523434.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-68355785-C-A is described in Lovd as [Pathogenic]. Variant chr16-68355785-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRMT7 | NM_019023.5 | c.1713C>A | p.Cys571Ter | stop_gained | 17/19 | ENST00000441236.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRMT7 | ENST00000441236.3 | c.1713C>A | p.Cys571Ter | stop_gained | 17/19 | 1 | NM_019023.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246522Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133958
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459240Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 725946
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Acanthosis nigricans;C0020473:Hyperlipidemia;C0021655:Insulin resistance;C0028754:Obesity;C0036857:Intellectual disability, severe;C0085271:Self-injurious behavior;C0221357:Brachydactyly;C0262444:Abnormality of the dentition;C0266295:Renal hypoplasia;C0349588:Short stature;C0410528:Skeletal dysplasia;C0424503:Abnormal facial shape;C1184923:Lumbar hyperlordosis;C1837084:Short metacarpal;C2711227:Hepatic steatosis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at