Variant chr12-3540631-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019854.5(PRMT8):c.101C>T(p.Pro34Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000444 in 1,577,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P34P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

PRMT8
NM_019854.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1318607).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT8	NM_019854.5 linkuse as main transcript	c.101C>T	p.Pro34Leu	missense_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.101C>T	p.Pro34Leu	missense_variant	2/10	1	NM_019854.5	P1	Q9NR22-1
PRMT8	ENST00000452611.6 linkuse as main transcript	c.74C>T	p.Pro25Leu	missense_variant	2/10	1			Q9NR22-2
PRMT8	ENST00000261252.4 linkuse as main transcript	n.520C>T		non_coding_transcript_exon_variant	2/12	2
PRMT8	ENST00000543701.5 linkuse as main transcript	n.468C>T		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248146

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134176

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000421

AC:

AN:

1425458

Hom.:

Cov.:

AF XY:

0.00000703

AC XY:

AN XY:

710826

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.101C>T (p.P34L) alteration is located in exon 2 (coding exon 2) of the PRMT8 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the proline (P) at amino acid position 34 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.0059

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.081

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.010

D;T

Polyphen

0.0

B;B

Vest4

0.42

MutPred

0.25

.;Loss of glycosylation at P34 (P = 0.0246);

MVP

0.22

MPC

0.24

ClinPred

0.80

GERP RS

5.5

Varity_R

0.056

gMVP

0.47

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