rs3791185

Variant names:

• chr1-107058247-G-A
• rs3791185
• NM_018137.3:c.*404G>A

Variant summary

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

The NM_018137.3(PRMT6):​c.*404G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 282,160 control chromosomes in the GnomAD database, including 4,223 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 0.15 (1971 hom., cov: 32)
  • Exomes 𝑓: 0.18 (2252 hom.)
• Consequence: PRMT6 NM_018137.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 11 publications found

Genes affected

PRMT6 (HGNC:18241): (protein arginine methyltransferase 6) The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT6	NM_018137.3	c.*404G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000370078.2	NP_060607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRMT6	ENST00000370078.2	c.*404G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_018137.3	ENSP00000359095.1
PRMT6	ENST00000649727.1	n.471+340G>A		intron_variant	Intron 1 of 1
PRMT6	ENST00000650338.1	n.*64+340G>A		intron_variant	Intron 1 of 2			ENSP00000497826.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22037 AN: 151900 Hom.: 1971 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.179 AC: 23233 AN: 130142 Hom.: 2252 Cov.: 0 AF XY: 0.178 AC XY: 12142 AN XY: 68262

African (AFR) AF: 0.0272 AC: 100 AN: 3680

American (AMR) AF: 0.142 AC: 626 AN: 4416

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 445 AN: 2952

East Asian (EAS) AF: 0.151 AC: 738 AN: 4888

South Asian (SAS) AF: 0.159 AC: 2972 AN: 18720

European-Finnish (FIN) AF: 0.243 AC: 4817 AN: 19832

Middle Eastern (MID) AF: 0.142 AC: 55 AN: 386

European-Non Finnish (NFE) AF: 0.180 AC: 12458 AN: 69350

Other (OTH) AF: 0.173 AC: 1022 AN: 5918

GnomAD4 genome AF: 0.145 AC: 22046 AN: 152018 Hom.: 1971 Cov.: 32 AF XY: 0.149 AC XY: 11093 AN XY: 74320

African (AFR) AF: 0.0343 AC: 1425 AN: 41496

American (AMR) AF: 0.154 AC: 2352 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.147 AC: 761 AN: 5164

South Asian (SAS) AF: 0.179 AC: 864 AN: 4814

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10560

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12834 AN: 67934

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.166 Hom.: 3156

Bravo AF: 0.130

Asia WGS AF: 0.145 AC: 505 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	4.4
DANN	Benign	0.68
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3791185; hg19: chr1-107600869;