1-107056951-C-G

Variant names:

• chr1-107056951-C-G
• rs368599166
• NM_018137.3:c.236C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018137.3(PRMT6):​c.236C>G​(p.Ala79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A79V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRMT6 NM_018137.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09903231).

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.236C>G	p.Ala79Gly	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.236C>G	p.Ala79Gly	missense	Exon 1 of 1	ENSP00000359095.1	Q96LA8-1
	PRMT6	ENST00000650338.1		n.50C>G		non_coding_transcript_exon	Exon 1 of 3	ENSP00000497826.1	A0A3B3ITK4
	ENSG00000294279	ENST00000722404.1		n.554G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460106 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726120

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111000

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N
PhyloP100		2.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.062
Sift	Benign	0.34	T
Sift4G	Benign	0.38	T
Polyphen		0.012	B
Vest4		0.096
MutPred		0.39		Loss of ubiquitination at K84 (P = 0.1278)
MVP		0.26
MPC		0.73
ClinPred		0.52	D
GERP RS		5.1
PromoterAI		0.075	Neutral
Varity_R		0.31
gMVP		0.54
Mutation Taster		=75/25	polymorphism

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: rs368599166; hg19: chr1-107599573;