chr1-107056824-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_018137.3(PRMT6):​c.109C>T​(p.Arg37Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRMT6
NM_018137.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375
Variant links:
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 2 ACMG points.

PM1
In a modified_residue Asymmetric dimethylarginine; by autocatalysis (size 0) in uniprot entity ANM6_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1860244).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRMT6NM_018137.3 linkc.109C>T p.Arg37Trp missense_variant Exon 1 of 1 ENST00000370078.2 NP_060607.2 Q96LA8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRMT6ENST00000370078.2 linkc.109C>T p.Arg37Trp missense_variant Exon 1 of 1 6 NM_018137.3 ENSP00000359095.1 Q96LA8-1
PRMT6ENST00000650338.1 linkn.-78C>T upstream_gene_variant ENSP00000497826.1 A0A3B3ITK4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1451380
Hom.:
0
Cov.:
31
AF XY:
0.00000416
AC XY:
3
AN XY:
721086
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Benign
0.92
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D
Sift4G
Benign
0.11
T
Polyphen
0.95
P
Vest4
0.24
MutPred
0.39
Gain of loop (P = 0.0435);
MVP
0.36
MPC
0.71
ClinPred
0.57
D
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.60

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: rs771493722; hg19: chr1-107599446; API