chr12-3580518-A-C

Position:

• chr12-3580518-A-C

Variant summary

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

The NM_019854.5(PRMT8):​c.829-2540A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,232 control chromosomes in the GnomAD database, including 1,360 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 0.12 (1360 hom., cov: 32)
• Consequence: PRMT8 NM_019854.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT8	NM_019854.5	c.829-2540A>C		intron_variant		ENST00000382622.4	NP_062828.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRMT8	ENST00000382622.4	c.829-2540A>C		intron_variant		1	NM_019854.5	ENSP00000372067	P1
PRMT8	ENST00000452611.6	c.802-2540A>C		intron_variant		1		ENSP00000414507
PRMT8	ENST00000261252.4	n.1511-2603A>C		intron_variant, non_coding_transcript_variant		2
PRMT8	ENST00000543701.5	n.4755-2540A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18830 AN: 152114 Hom.: 1360 Cov.: 32

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.0880

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.124 AC: 18844 AN: 152232 Hom.: 1360 Cov.: 32 AF XY: 0.119 AC XY: 8826 AN XY: 74420

Gnomad4 AFR AF: 0.0952

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0223

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.159

Alfa AF: 0.130 Hom.: 483

Bravo AF: 0.128

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.69

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: rs10491968; hg19: chr12-3689684; COSMIC: COSV54219773;