12-3515931-T-C

Position:

• chr12-3515931-T-C

Variant summary

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

The ENST00000382622.4(PRMT8):​c.75+24231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,178 control chromosomes in the GnomAD database, including 20,626 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 0.52 (20626 hom., cov: 33)
• Consequence: PRMT8 ENST00000382622.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRMT8	NM_019854.5	c.75+24231T>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.75+24231T>C		intron_variant		1	NM_019854.5	ENSP00000372067	P1
PRMT8	ENST00000452611.6	c.49-24675T>C		intron_variant		1		ENSP00000414507
PRMT8	ENST00000543701.5	n.442+24231T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78630 AN: 152060 Hom.: 20601 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.517 AC: 78713 AN: 152178 Hom.: 20626 Cov.: 33 AF XY: 0.513 AC XY: 38162 AN XY: 74392

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.539

Alfa AF: 0.487 Hom.: 23257

Bravo AF: 0.526

Asia WGS AF: 0.539 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.53

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: rs7972248; hg19: chr12-3625097;