Variant 19-49682052-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001536.6(PRMT1):c.335G>A(p.Arg112His) variant causes a missense change. The variant allele was found at a frequency of 0.0000787 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

PRMT1
NM_001536.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

PRMT1 (HGNC:5187): (protein arginine methyltransferase 1) This gene encodes a member of the protein arginine N-methyltransferase (PRMT) family. Post-translational modification of target proteins by PRMTs plays an important regulatory role in many biological processes, whereby PRMTs methylate arginine residues by transferring methyl groups from S-adenosyl-L-methionine to terminal guanidino nitrogen atoms. The encoded protein is a type I PRMT and is responsible for the majority of cellular arginine methylation activity. Increased expression of this gene may play a role in many types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

PRMT1 links:

PRMT1 (HGNC:):

PRMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058085322).

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT1	NM_001536.6 linkuse as main transcript	c.335G>A	p.Arg112His	missense_variant	4/11	ENST00000454376.7	NP_001527.3	Q99873-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT1	ENST00000454376.7 linkuse as main transcript	c.335G>A	p.Arg112His	missense_variant	4/11	1	NM_001536.6	ENSP00000406162.2		Q99873-1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000838

AC:

AN:

250556

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.000809

Gnomad AMR exome

AF:

0.0000868

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:

0.0000265

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461728

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000302

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000940

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

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

Aug 20, 2024

The c.335G>A (p.R112H) alteration is located in exon 4 (coding exon 4) of the PRMT1 gene. This alteration results from a G to A substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a histidine (H). 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

0.28

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

.;T;.;T;.;.;.;T;.

Eigen

Benign

0.0080

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.058

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.6

D;N;D;N;N;.;N;D;D

REVEL

Benign

0.083

Sift

Uncertain

0.0050

D;D;D;D;D;.;D;D;D

Sift4G

Uncertain

0.025

D;D;D;D;D;D;D;D;D

Polyphen

0.027

.;B;.;.;.;.;.;.;.

Vest4

0.23, 0.22, 0.28, 0.23

MVP

0.32

MPC

1.6

ClinPred

0.048

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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