19-49685899-G-T

Variant names:

• chr19-49685899-G-T
• rs10415880
• NM_001536.6:c.760-194G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001536.6(PRMT1):​c.760-194G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 1,257,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: PRMT1 NM_001536.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 0 publications found

Genes affected

PRMT1 (HGNC:5187): (protein arginine methyltransferase 1) This gene encodes a member of the protein arginine N-methyltransferase (PRMT) family. Post-translational modification of target proteins by PRMTs plays an important regulatory role in many biological processes, whereby PRMTs methylate arginine residues by transferring methyl groups from S-adenosyl-L-methionine to terminal guanidino nitrogen atoms. The encoded protein is a type I PRMT and is responsible for the majority of cellular arginine methylation activity. Increased expression of this gene may play a role in many types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001536.6. 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
	PRMT1	NM_001536.6	MANE Select	c.760-194G>T		intron	N/A	NP_001527.3
	PRMT1	NM_198318.5		c.706-194G>T		intron	N/A	NP_938074.2
	PRMT1	NM_001207042.3		c.502-194G>T		intron	N/A	NP_001193971.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT1	ENST00000454376.7	TSL:1 MANE Select	c.760-194G>T		intron	N/A	ENSP00000406162.2
	PRMT1	ENST00000391851.8	TSL:1	c.706-194G>T		intron	N/A	ENSP00000375724.4
	PRMT1	ENST00000911948.1		c.760-194G>T		intron	N/A	ENSP00000582007.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000398 AC: 5 AN: 1257500 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 608280

African (AFR) AF: 0.00 AC: 0 AN: 27646

American (AMR) AF: 0.00 AC: 0 AN: 17186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18196

East Asian (EAS) AF: 0.00 AC: 0 AN: 33064

South Asian (SAS) AF: 0.00 AC: 0 AN: 59882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3494

European-Non Finnish (NFE) AF: 0.00000492 AC: 5 AN: 1017242

Other (OTH) AF: 0.00 AC: 0 AN: 51942

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.63
PhyloP100		-0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10415880; hg19: chr19-50189156;