4-147654033-T-A

Position:

• chr4-147654033-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138364.4(PRMT9):​c.1864A>T​(p.Ile622Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRMT9 NM_138364.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89

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]

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

PRMT9 (HGNC:):

ACMG classification

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=0.121935606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT9	NM_138364.4	c.1864A>T	p.Ile622Leu	missense_variant	9/12	ENST00000322396.7	NP_612373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT9	ENST00000322396.7	c.1864A>T	p.Ile622Leu	missense_variant	9/12	1	NM_138364.4	ENSP00000314396.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.1864A>T (p.I622L) alteration is located in exon 9 (coding exon 9) of the PRMT9 gene. This alteration results from a A to T substitution at nucleotide position 1864, causing the isoleucine (I) at amino acid position 622 to be replaced by a leucine (L). 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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.0072
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.041
Sift	Benign	0.56	T
Sift4G	Benign	0.92	T
Polyphen		0.0060	B
Vest4		0.23
MutPred		0.32		Gain of disorder (P = 0.1744);
MVP		0.29
MPC		0.23
ClinPred		0.33	T
GERP RS		6.2
Varity_R		0.24
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-148575184;