12-3540764-C-T

Variant names:

• chr12-3540764-C-T
• rs74678751
• NM_019854.5:c.234C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_019854.5(PRMT8):​c.234C>T​(p.Asp78Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,052 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: PRMT8 NM_019854.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 12-3540764-C-T is Benign according to our data. Variant chr12-3540764-C-T is described in ClinVar as Benign. ClinVar VariationId is 776687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00778 (1185/152336) while in subpopulation AFR AF = 0.0252 (1048/41566). AF 95% confidence interval is 0.0239. There are 9 homozygotes in GnomAd4. There are 543 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1185 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT8	NM_019854.5	MANE Select	c.234C>T	p.Asp78Asp	synonymous	Exon 2 of 10	NP_062828.3
	PRMT8	NM_001256536.1		c.207C>T	p.Asp69Asp	synonymous	Exon 2 of 10	NP_001243465.1	Q9NR22-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT8	ENST00000382622.4	TSL:1 MANE Select	c.234C>T	p.Asp78Asp	synonymous	Exon 2 of 10	ENSP00000372067.3	Q9NR22-1
	PRMT8	ENST00000452611.6	TSL:1	c.207C>T	p.Asp69Asp	synonymous	Exon 2 of 10	ENSP00000414507.2	Q9NR22-2
	PRMT8	ENST00000927113.1		c.234C>T	p.Asp78Asp	synonymous	Exon 2 of 10	ENSP00000597172.1

Frequencies

GnomAD3 genomes AF: 0.00778 AC: 1184 AN: 152218 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00233 AC: 585 AN: 251114 AF XY: 0.00189

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00428

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00102 AC: 1491 AN: 1461716 Hom.: 19 Cov.: 35 AF XY: 0.000948 AC XY: 689 AN XY: 727144

African (AFR) AF: 0.0260 AC: 869 AN: 33478

American (AMR) AF: 0.00262 AC: 117 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00456 AC: 119 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00128 AC: 110 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111916

Other (OTH) AF: 0.00260 AC: 157 AN: 60388

GnomAD4 genome AF: 0.00778 AC: 1185 AN: 152336 Hom.: 9 Cov.: 31 AF XY: 0.00729 AC XY: 543 AN XY: 74482

African (AFR) AF: 0.0252 AC: 1048 AN: 41566

American (AMR) AF: 0.00457 AC: 70 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68032

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00436 Hom.: 2

Bravo AF: 0.00872

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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: rs74678751; hg19: chr12-3649930;