Variant chr4-147638651-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000322396.7(PRMT9):c.2419T>A(p.Ser807Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRMT9
ENST00000322396.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.80

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:

PRMT9 (HGNC:):

PRMT9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT9	NM_138364.4 linkuse as main transcript	c.2419T>A	p.Ser807Thr	missense_variant	12/12	ENST00000322396.7	NP_612373.2	Q6P2P2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT9	ENST00000322396.7 linkuse as main transcript	c.2419T>A	p.Ser807Thr	missense_variant	12/12	1	NM_138364.4	ENSP00000314396.6		Q6P2P2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251226

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461216

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

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

Dec 03, 2021

The c.2419T>A (p.S807T) alteration is located in exon 12 (coding exon 12) of the PRMT9 gene. This alteration results from a T to A substitution at nucleotide position 2419, causing the serine (S) at amino acid position 807 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Uncertain

0.027

Sift4G

Uncertain

0.034

Polyphen

1.0

Vest4

0.42

MVP

0.45

MPC

0.76

ClinPred

0.82

GERP RS

5.5

Varity_R

0.57

gMVP

0.66

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