12-3538926-G-A

Variant names:

• chr12-3538926-G-A
• rs7962508
• NM_019854.5:c.76-1680G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019854.5(PRMT8):​c.76-1680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,124 control chromosomes in the GnomAD database, including 49,589 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 0.80 (49589 hom., cov: 32)
• Consequence: PRMT8 NM_019854.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019854.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT8	NM_019854.5	MANE Select	c.76-1680G>A		intron	N/A	NP_062828.3
	PRMT8	NM_001256536.1		c.49-1680G>A		intron	N/A	NP_001243465.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT8	ENST00000382622.4	TSL:1 MANE Select	c.76-1680G>A		intron	N/A	ENSP00000372067.3
	PRMT8	ENST00000452611.6	TSL:1	c.49-1680G>A		intron	N/A	ENSP00000414507.2
	PRMT8	ENST00000261252.4	TSL:2	n.494+219G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122068 AN: 152006 Hom.: 49561 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.803 AC: 122150 AN: 152124 Hom.: 49589 Cov.: 32 AF XY: 0.806 AC XY: 59917 AN XY: 74372

African (AFR) AF: 0.682 AC: 28273 AN: 41472

American (AMR) AF: 0.884 AC: 13525 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2999 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4858 AN: 5168

South Asian (SAS) AF: 0.898 AC: 4327 AN: 4820

European-Finnish (FIN) AF: 0.798 AC: 8430 AN: 10570

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56939 AN: 68008

Other (OTH) AF: 0.827 AC: 1749 AN: 2116

Alfa AF: 0.837 Hom.: 100657

Bravo AF: 0.806

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7962508; hg19: chr12-3648092;