Genetic Variant ENSG00000294279:n.869T>A (chr1-107056636-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000722404.1(ENSG00000294279):n.869T>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.321 in 1,440,018 control chromosomes in the GnomAD database, including 76,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5827 hom., cov: 33)

Exomes 𝑓: 0.33 ( 70402 hom. )

Consequence

ENSG00000294279
ENST00000722404.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.21

Publications

16 publications found

Variant links:

COSMIC-nc: COSV63656520

Genes affected

ENSG00000294279 (HGNC:):

ENSG00000294279 links:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT6	NM_018137.3 link	c.-80A>T		upstream_gene_variant		ENST00000370078.2	NP_060607.2	Q96LA8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294279	ENST00000722404.1 link	n.869T>A		non_coding_transcript_exon_variant	Exon 1 of 1
PRMT6	ENST00000370078.2 link	c.-80A>T		upstream_gene_variant		6	NM_018137.3	ENSP00000359095.1		Q96LA8-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38666

AN:

152038

Hom.:

5822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.245

GnomAD4 exome

AF:

0.329

AC:

423258

AN:

1287860

Hom.:

70402

Cov.:

AF XY:

0.330

AC XY:

206135

AN XY:

625398

show subpopulations

African (AFR)

AF:

0.0735

AC:

2055

AN:

27970

American (AMR)

AF:

0.244

AC:

4781

AN:

19588

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

5033

AN:

18832

East Asian (EAS)

AF:

0.284

AC:

9904

AN:

34856

South Asian (SAS)

AF:

0.329

AC:

20555

AN:

62476

European-Finnish (FIN)

AF:

0.292

AC:

12642

AN:

43226

Middle Eastern (MID)

AF:

0.288

AC:

1037

AN:

3606

European-Non Finnish (NFE)

AF:

0.342

AC:

350477

AN:

1024124

Other (OTH)

AF:

0.315

AC:

16774

AN:

53182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14486

28972

43458

57944

72430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11688

23376

35064

46752

58440

<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:

0.254

AC:

38678

AN:

152158

Hom.:

5827

Cov.:

AF XY:

0.253

AC XY:

18841

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0849

AC:

3529

AN:

41560

American (AMR)

AF:

0.250

AC:

3829

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

925

AN:

3468

East Asian (EAS)

AF:

0.301

AC:

1547

AN:

5144

South Asian (SAS)

AF:

0.331

AC:

1598

AN:

4824

European-Finnish (FIN)

AF:

0.292

AC:

3095

AN:

10592

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23240

AN:

67962

Other (OTH)

AF:

0.248

AC:

523

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1468

2935

4403

5870

7338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.168

Hom.:

368

Bravo

AF:

0.241

Asia WGS

AF:

0.315

AC:

1096

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

4.2

PromoterAI

-0.42

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over