4-147654049-AC-GT

Variant names:

• chr4-147654049-AC-GT
• NM_138364.4:c.1847_1848delGTinsAC
• PRMT9 p.Arg616His

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 0P and 0B.

The NM_138364.4(PRMT9):​c.1847_1848delGTinsAC​(p.Arg616His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRMT9 NM_138364.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138364.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT9	NM_138364.4	MANE Select	c.1847_1848delGTinsAC	p.Arg616His	missense	N/A	NP_612373.2
	PRMT9	NM_001304458.2		c.1508_1509delGTinsAC	p.Arg503His	missense	N/A	NP_001291387.1	Q6P2P2-2
	PRMT9	NM_001350142.2		c.1508_1509delGTinsAC	p.Arg503His	missense	N/A	NP_001337071.1	Q6P2P2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT9	ENST00000322396.7	TSL:1 MANE Select	c.1847_1848delGTinsAC	p.Arg616His	missense	N/A	ENSP00000314396.6	Q6P2P2-1
	TMEM184C	ENST00000508208.5	TSL:1	c.780-17818_780-17817delACinsGT		intron	N/A	ENSP00000425940.1	A0A0C4DGC8
	PRMT9	ENST00000960614.1		c.1847_1848delGTinsAC	p.Arg616His	missense	N/A	ENSP00000630673.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-148575200;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline