Variant 12-3540627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019854.5(PRMT8):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,420,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

PRMT8
NM_019854.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12708554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT8	NM_019854.5 link	c.97C>T	p.Pro33Ser	missense_variant	2/10	ENST00000382622.4	NP_062828.3	Q9NR22-1Q59GT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRMT8	ENST00000382622.4 link	c.97C>T	p.Pro33Ser	missense_variant	2/10	1	NM_019854.5	ENSP00000372067.3	Q9NR22-1
PRMT8	ENST00000452611.6 link	c.70C>T	p.Pro24Ser	missense_variant	2/10	1		ENSP00000414507.2	Q9NR22-2
PRMT8	ENST00000261252.4 link	n.516C>T		non_coding_transcript_exon_variant	2/12	2
PRMT8	ENST00000543701.5 link	n.464C>T		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149630

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000421

AC:

AN:

237350

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000315

AC:

AN:

1270604

Hom.:

Cov.:

AF XY:

0.00000469

AC XY:

AN XY:

639754

show subpopulations

Gnomad4 AFR exome

AF:

0.0000341

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000834

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149630

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72904

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:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 04, 2024

The c.97C>T (p.P33S) 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 97, causing the proline (P) at amino acid position 33 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

.;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.088

Sift

Benign

0.26

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0040

B;B

Vest4

0.44

MutPred

0.15

.;Loss of catalytic residue at P33 (P = 9e-04);

MVP

0.22

MPC

0.24

ClinPred

0.73

GERP RS

5.5

Varity_R

0.071

gMVP

0.44

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