NM_018137.3:c.25C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_018137.3(PRMT6):c.25C>G(p.Leu9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,533,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PRMT6
NM_018137.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.779

Publications

3 publications found

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:

ENSG00000294279 (HGNC:):

ENSG00000294279 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004734814).

BP6

Variant 1-107056740-C-G is Benign according to our data. Variant chr1-107056740-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3042273.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018137.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT6	NM_018137.3	MANE Select	c.25C>G	p.Leu9Val	missense	Exon 1 of 1	NP_060607.2	Q96LA8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRMT6	ENST00000370078.2	TSL:6 MANE Select	c.25C>G	p.Leu9Val	missense	Exon 1 of 1	ENSP00000359095.1	Q96LA8-1
ENSG00000294279	ENST00000722404.1		n.765G>C		non_coding_transcript_exon	Exon 1 of 1
PRMT6	ENST00000650338.1		n.-162C>G		upstream_gene	N/A	ENSP00000497826.1	A0A3B3ITK4

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

170

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000479

GnomAD2 exomes

AF:

0.000274

AC:

AN:

138646

AF XY:

0.000176

show subpopulations

Gnomad AFR exome

AF:

0.00500

Gnomad AMR exome

AF:

0.0000447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000259

GnomAD4 exome

AF:

0.000122

AC:

169

AN:

1381268

Hom.:

Cov.:

AF XY:

0.0000986

AC XY:

AN XY:

679486

show subpopulations

African (AFR)

AF:

0.00475

AC:

147

AN:

30976

American (AMR)

AF:

0.000120

AC:

AN:

33258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23774

East Asian (EAS)

AF:

0.00

AC:

AN:

35520

South Asian (SAS)

AF:

0.00

AC:

AN:

76942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48166

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1070064

Other (OTH)

AF:

0.000245

AC:

AN:

57030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00112

AC:

170

AN:

152312

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00394

AC:

164

AN:

41576

American (AMR)

AF:

0.000327

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.00135

ExAC

AF:

0.000111

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PRMT6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.041

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.48

M_CAP

Benign

0.013

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

PhyloP100

0.78

PrimateAI

Benign

0.44

PROVEAN

Benign

0.13

REVEL

Benign

0.043

Sift

Benign

0.096

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.13

MVP

0.21

MPC

1.3

ClinPred

0.030

GERP RS

0.33

PromoterAI

0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.084

gMVP

0.50

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over