Genetic Variant PRMT3:p.Arg244Leu (chr11-20402944-G-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_005788.4(PRMT3):c.731G>T(p.Arg244Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R244Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PRMT3
NM_005788.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.56

Publications

0 publications found

Variant links:

Genes affected

PRMT3 (HGNC:30163): (protein arginine methyltransferase 3) This gene belongs to the protein arginine methyltransferase (PRMT) family. The encoded enzyme catalyzes the methylation of guanidino nitrogens of arginyl residues of proteins. The enzyme acts on 40S ribosomal protein S2 (rpS2), which is its major in-vivo substrate, and is involved in the proper maturation of the 80S ribosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

PRMT3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT3	NM_005788.4 link	c.731G>T	p.Arg244Leu	missense_variant	Exon 8 of 16	ENST00000331079.11	NP_005779.1	O60678-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRMT3	ENST00000331079.11 link	c.731G>T	p.Arg244Leu	missense_variant	Exon 8 of 16	1	NM_005788.4	ENSP00000331879.6	O60678-1
PRMT3	ENST00000330796.9 link	n.*454G>T		non_coding_transcript_exon_variant	Exon 7 of 15	1		ENSP00000329586.5	E9PLF6
PRMT3	ENST00000330796.9 link	n.*454G>T		3_prime_UTR_variant	Exon 7 of 15	1		ENSP00000329586.5	E9PLF6
PRMT3	ENST00000437750.2 link	c.545G>T	p.Arg182Leu	missense_variant	Exon 6 of 14	2		ENSP00000397766.2	O60678-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251272

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456640

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33314

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107460

Other (OTH)

AF:

0.00

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.1

M;.

PhyloP100

9.6

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.60

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.75

P;D

Vest4

0.91

MutPred

0.58

Loss of disorder (P = 0.0738);.;

MVP

0.67

MPC

0.38

ClinPred

0.99

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.90

gMVP

0.84

Mutation Taster

=17/83

disease causing

(source)

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

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11-20402944-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over