rs2232016

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018137.3(PRMT6):​c.581C>A​(p.Ala194Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A194V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRMT6
NM_018137.3 missense

Scores

5
12
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRMT6NM_018137.3 linkc.581C>A p.Ala194Asp 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.581C>A p.Ala194Asp missense_variant Exon 1 of 1 6 NM_018137.3 ENSP00000359095.1 Q96LA8-1
PRMT6ENST00000650338.1 linkn.395C>A non_coding_transcript_exon_variant Exon 1 of 3 ENSP00000497826.1 A0A3B3ITK4
PRMT6ENST00000649727.1 linkn.-141C>A upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248050
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134884
show subpopulations
Gnomad AFR exome
AF:
0.0000655
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461666
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727134
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.4
D
REVEL
Uncertain
0.47
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.98
D
Vest4
0.84
MutPred
0.48
Loss of helix (P = 0.0626);
MVP
0.45
MPC
2.1
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.96
gMVP
0.94

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: rs2232016; hg19: chr1-107599918; API