Genetic Variant PRMT9:p.Ile736Val (chr4-147639076-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138364.4(PRMT9):c.2206A>G(p.Ile736Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. I736L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRMT9
NM_138364.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

PRMT9 (HGNC:25099): (protein arginine methyltransferase 9) This gene encodes a type II methyltransferase. 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 the guanidino nitrogen atoms of arginine. The protein encoded by this gene methylates spliceosome associated protein 145 to regulate alternative splicing and acts as a modulator of small nuclear ribonucleoprotein maturation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2017]

PRMT9 links:

TMEM184C (HGNC:25587): (transmembrane protein 184C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM184C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041380525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT9	NM_138364.4 link	c.2206A>G	p.Ile736Val	missense_variant	Exon 11 of 12	ENST00000322396.7	NP_612373.2	Q6P2P2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRMT9	ENST00000322396.7 link	c.2206A>G	p.Ile736Val	missense_variant	Exon 11 of 12	1	NM_138364.4	ENSP00000314396.6		Q6P2P2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461128

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111526

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.0

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.026

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.73

M_CAP

Benign

0.0042

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.050

PhyloP100

1.3

PrimateAI

Benign

0.26

PROVEAN

Benign

0.34

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.056

MutPred

0.38

Loss of catalytic residue at I736 (P = 0.0347);

MVP

0.12

MPC

0.18

ClinPred

0.13

GERP RS

3.1

Varity_R

0.059

gMVP

0.34

Mutation Taster

=85/15

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over