Variant chr12-3540764-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_019854.5(PRMT8):c.234C>T(p.Asp78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,052 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 19 hom. )

Consequence

PRMT8
NM_019854.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

PRMT8 (HGNC:5188): (protein arginine methyltransferase 8) Arginine methylation is a widespread posttranslational modification mediated by arginine methyltransferases, such as PRMT8. Arginine methylation is involved in a number of cellular processes, including DNA repair, RNA transcription, signal transduction, protein compartmentalization, and possibly protein translation (Lee et al., 2005 [PubMed 16051612]).[supplied by OMIM, Mar 2008]

PRMT8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-3540764-C-T is Benign according to our data. Variant chr12-3540764-C-T is described in ClinVar as [Benign]. Clinvar id is 776687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00778 (1185/152336) while in subpopulation AFR AF= 0.0252 (1048/41566). AF 95% confidence interval is 0.0239. There are 9 homozygotes in gnomad4. There are 543 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT8	NM_019854.5 linkuse as main transcript	c.234C>T	p.Asp78=	synonymous_variant	2/10	ENST00000382622.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT8	ENST00000382622.4 linkuse as main transcript	c.234C>T	p.Asp78=	synonymous_variant	2/10	1	NM_019854.5	P1	Q9NR22-1
PRMT8	ENST00000452611.6 linkuse as main transcript	c.207C>T	p.Asp69=	synonymous_variant	2/10	1			Q9NR22-2
PRMT8	ENST00000261252.4 linkuse as main transcript	n.653C>T		non_coding_transcript_exon_variant	2/12	2
PRMT8	ENST00000543701.5 linkuse as main transcript	n.601C>T		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.00778

AC:

1184

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00233

AC:

585

AN:

251114

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00102

AC:

1491

AN:

1461716

Hom.:

Cov.:

AF XY:

0.000948

AC XY:

689

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00456

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000782

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00778

AC:

1185

AN:

152336

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

543

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.00457

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00452

Hom.:

Bravo

AF:

0.00872

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.73

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