Variant chr1-107057296-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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]

PRMT6 links:

Genome browser will be placed here

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 linkuse as main transcript	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 linkuse as main transcript	c.581C>T	p.Ala194Val	missense_variant	1/1		NM_018137.3	P1	Q96LA8-1
PRMT6	ENST00000650338.1 linkuse as main transcript	c.395C>T	p.Ala132Val	missense_variant, NMD_transcript_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22784

AN:

152174

Hom.:

2194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.176

AC:

43565

AN:

248050

Hom.:

4297

AF XY:

0.184

AC XY:

24874

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.0947

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.233

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.203

AC:

296492

AN:

1461634

Hom.:

31106

Cov.:

AF XY:

0.205

AC XY:

149022

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0966

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.150

AC:

22776

AN:

152292

Hom.:

2193

Cov.:

AF XY:

0.149

AC XY:

11115

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0375

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.196

Hom.:

7676

Bravo

AF:

0.139

TwinsUK

AF:

0.212

AC:

785

ALSPAC

AF:

0.218

AC:

841

ESP6500AA

AF:

0.0443

AC:

175

ESP6500EA

AF:

0.207

AC:

1727

ExAC

AF:

0.177

AC:

21360

Asia WGS

AF:

0.202

AC:

703

AN:

3478

EpiCase

AF:

0.213

EpiControl

AF:

0.220

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.0000041

P;P;P

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.13

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.017

Polyphen

0.61

Vest4

0.19

MPC

1.7

ClinPred

0.038

GERP RS

5.5

Varity_R

0.77

gMVP

0.80

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over