chr1-107057296-C-T

Variant names:

• chr1-107057296-C-T
• rs2232016
• NM_018137.3:c.581C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_018137.3(PRMT6):​c.581C>T​(p.Ala194Val) variant causes a missense change. The variant allele was found at a frequency of 0.198 in 1,613,926 control chromosomes in the GnomAD database, including 33,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2193 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31106 hom.)
• Consequence: PRMT6 NM_018137.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.93
• Publications: 34 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]

ENSG00000294279 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001822114).
• BP6: Variant 1-107057296-C-T is Benign according to our data. Variant chr1-107057296-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060084.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018137.3. 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
	PRMT6	NM_018137.3	MANE Select	c.581C>T	p.Ala194Val	missense	Exon 1 of 1	NP_060607.2	Q96LA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT6	ENST00000370078.2	TSL:6 MANE Select	c.581C>T	p.Ala194Val	missense	Exon 1 of 1	ENSP00000359095.1	Q96LA8-1
	PRMT6	ENST00000650338.1		n.395C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000497826.1	A0A3B3ITK4
	ENSG00000294279	ENST00000722404.1		n.209G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22784 AN: 152174 Hom.: 2194 Cov.: 33

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.176 AC: 43565 AN: 248050 AF XY: 0.184

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.0947

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.150

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.203 AC: 296492 AN: 1461634 Hom.: 31106 Cov.: 33 AF XY: 0.205 AC XY: 149022 AN XY: 727114

African (AFR) AF: 0.0314 AC: 1051 AN: 33480

American (AMR) AF: 0.0966 AC: 4322 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4243 AN: 26134

East Asian (EAS) AF: 0.176 AC: 6996 AN: 39700

South Asian (SAS) AF: 0.227 AC: 19581 AN: 86250

European-Finnish (FIN) AF: 0.171 AC: 9088 AN: 53216

Middle Eastern (MID) AF: 0.182 AC: 1050 AN: 5768

European-Non Finnish (NFE) AF: 0.215 AC: 238584 AN: 1111972

Other (OTH) AF: 0.192 AC: 11577 AN: 60392

GnomAD4 genome AF: 0.150 AC: 22776 AN: 152292 Hom.: 2193 Cov.: 33 AF XY: 0.149 AC XY: 11115 AN XY: 74464

African (AFR) AF: 0.0375 AC: 1560 AN: 41582

American (AMR) AF: 0.120 AC: 1830 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3466

East Asian (EAS) AF: 0.158 AC: 818 AN: 5164

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4830

European-Finnish (FIN) AF: 0.166 AC: 1757 AN: 10612

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14617 AN: 68016

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.187 Hom.: 9739

Bravo AF: 0.139

TwinsUK AF: 0.212 AC: 785

ALSPAC AF: 0.218 AC: 841

ESP6500AA AF: 0.0443 AC: 175

ESP6500EA AF: 0.207 AC: 1727

ExAC AF: 0.177 AC: 21360

Asia WGS AF: 0.202 AC: 703 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.220

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRMT6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.9
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.017	D
Polyphen		0.61	P
Vest4		0.19
MPC		1.7
ClinPred		0.038	T
GERP RS		5.5
Varity_R		0.77
gMVP		0.80
Mutation Taster		=91/9	polymorphism (auto)

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: rs2232016; hg19: chr1-107599918; COSMIC: COSV63654957;