rs12299470

chr12-3528284-G-Achr12-3528284-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019854.5(PRMT8):c.76-12322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,834 control chromosomes in the GnomAD database, including 1,498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1498 hom., cov: 32)
• Consequence: PRMT8 NM_019854.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

PRMT8 (HGNC:5188): (protein arginine methyltransferase 8) Arginine methylation is a widespread posttranslational modification mediated by arginine methyltransferases, such as PRMT8. Arginine methylation is involved in a number of cellular processes, including DNA repair, RNA transcription, signal transduction, protein compartmentalization, and possibly protein translation (Lee et al., 2005 [PubMed 16051612]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT8	NM_019854.5	c.76-12322G>A		intron_variant		ENST00000382622.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT8	ENST00000382622.4	c.76-12322G>A		intron_variant		1	NM_019854.5	P1
PRMT8	ENST00000452611.6	c.49-12322G>A		intron_variant		1
PRMT8	ENST00000543701.5	n.443-12322G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19466 AN: 151716 Hom.: 1490 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.128 AC: 19493 AN: 151834 Hom.: 1498 Cov.: 32 AF XY: 0.129 AC XY: 9548 AN XY: 74192

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.137

Alfa AF: 0.108 Hom.: 731

Bravo AF: 0.142

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.9
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs12299470; hg19: chr12-3637450;