1-107057289-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018137.3(PRMT6):āc.574T>Cā(p.Phe192Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00023 in 1,613,960 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 (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 33)
Exomes š: 0.00024 ( 0 hom. )
Consequence
PRMT6
NM_018137.3 missense
NM_018137.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 4.00
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25062907).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRMT6 | NM_018137.3 | c.574T>C | p.Phe192Leu | missense_variant | 1/1 | ENST00000370078.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRMT6 | ENST00000370078.2 | c.574T>C | p.Phe192Leu | missense_variant | 1/1 | NM_018137.3 | P1 | ||
PRMT6 | ENST00000650338.1 | c.388T>C | p.Phe130Leu | missense_variant, NMD_transcript_variant | 1/3 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000886 AC: 22AN: 248362Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 135006
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GnomAD4 exome AF: 0.000239 AC: 350AN: 1461738Hom.: 0 Cov.: 32 AF XY: 0.000219 AC XY: 159AN XY: 727172
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.574T>C (p.F192L) alteration is located in exon 1 (coding exon 1) of the PRMT6 gene. This alteration results from a T to C substitution at nucleotide position 574, causing the phenylalanine (F) at amino acid position 192 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of helix (P = 0.028);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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