1-107057296-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_018137.3(PRMT6):c.581C>T(p.Ala194Val) variant causes a missense change. The variant allele was found at a frequency of 0.198 in 1,613,926 control chromosomes in the GnomAD database, including 33,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.15 ( 2193 hom., cov: 33)
Exomes 𝑓: 0.20 ( 31106 hom. )
Consequence
PRMT6
NM_018137.3 missense
NM_018137.3 missense
Scores
1
10
7
Clinical Significance
Conservation
PhyloP100: 4.93
Genes affected
PRMT6 (HGNC:18241): (protein arginine methyltransferase 6) The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.001822114).
BP6
Variant 1-107057296-C-T is Benign according to our data. Variant chr1-107057296-C-T is described in ClinVar as [Benign]. Clinvar id is 3060084.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRMT6 | NM_018137.3 | c.581C>T | p.Ala194Val | missense_variant | 1/1 | ENST00000370078.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRMT6 | ENST00000370078.2 | c.581C>T | p.Ala194Val | missense_variant | 1/1 | NM_018137.3 | P1 | ||
PRMT6 | ENST00000650338.1 | c.395C>T | p.Ala132Val | missense_variant, NMD_transcript_variant | 1/3 |
Frequencies
GnomAD3 genomes AF: 0.150 AC: 22784AN: 152174Hom.: 2194 Cov.: 33
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GnomAD3 exomes AF: 0.176 AC: 43565AN: 248050Hom.: 4297 AF XY: 0.184 AC XY: 24874AN XY: 134884
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GnomAD4 exome AF: 0.203 AC: 296492AN: 1461634Hom.: 31106 Cov.: 33 AF XY: 0.205 AC XY: 149022AN XY: 727114
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GnomAD4 genome AF: 0.150 AC: 22776AN: 152292Hom.: 2193 Cov.: 33 AF XY: 0.149 AC XY: 11115AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PRMT6-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 30, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MPC
ClinPred
T
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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