1-107056636-A-T

Position:

• chr1-107056636-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The 1-107056636-A-T variant causes a upstream gene change. The variant allele was found at a frequency of 0.321 in 1,440,018 control chromosomes in the GnomAD database, including 76,229 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 0.25 (5827 hom., cov: 33)
  • Exomes 𝑓: 0.33 (70402 hom.)
• Consequence: PRMT6 NM_018137.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT6	NM_018137.3			upstream_gene_variant		ENST00000370078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT6	ENST00000370078.2			upstream_gene_variant			NM_018137.3	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38666 AN: 152038 Hom.: 5822 Cov.: 33

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.329 AC: 423258 AN: 1287860 Hom.: 70402 Cov.: 26 AF XY: 0.330 AC XY: 206135 AN XY: 625398

Gnomad4 AFR exome AF: 0.0735

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.254 AC: 38678 AN: 152158 Hom.: 5827 Cov.: 33 AF XY: 0.253 AC XY: 18841 AN XY: 74406

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.248

Alfa AF: 0.168 Hom.: 368

Bravo AF: 0.241

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2232015; hg19: chr1-107599258; COSMIC: COSV63656520;