16-68354489-T-A

Variant names:

• chr16-68354489-T-A
• rs3785125
• NM_019023.5:c.1650+923T>A

Variant summary

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

The NM_019023.5(PRMT7):​c.1650+923T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,200 control chromosomes in the GnomAD database, including 23,815 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 0.55 (23814 hom., cov: 34)
  • Exomes 𝑓: 0.42 (1 hom.)
• Consequence: PRMT7 NM_019023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 4 publications found

Genes affected

PRMT7 (HGNC:25557): (protein arginine methyltransferase 7) This gene encodes a member of the protein arginine N-methyltransferase family of proteins. The encoded enzyme transfers single methyl groups to arginine residues to generate monomethylarginines on histone proteins as well as other protein substrates. This enzyme plays a role in a wide range of biological processes, including neuronal differentiation, male germ line imprinting, small nuclear ribonucleoprotein biogenesis, and regulation of the Wnt signaling pathway. Mutations in this gene underlie multiple related syndromes in human patients characterized by intellectual disability, short stature and other features. The encoded protein may promote breast cancer cell invasion and metastasis in human patients. [provided by RefSeq, May 2017]

PRMT7 Gene-Disease associations (from GenCC):

• short stature-brachydactyly-obesity-global developmental delay syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019023.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT7	NM_019023.5	MANE Select	c.1650+923T>A		intron	N/A	NP_061896.1
	PRMT7	NM_001351143.3		c.1650+923T>A		intron	N/A	NP_001338072.1
	PRMT7	NM_001351144.3		c.1653+923T>A		intron	N/A	NP_001338073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT7	ENST00000441236.3	TSL:1 MANE Select	c.1650+923T>A		intron	N/A	ENSP00000409324.2
	PRMT7	ENST00000567542.5	TSL:1	n.1774+923T>A		intron	N/A
	PRMT7	ENST00000568463.1	TSL:2	n.161T>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84349 AN: 152056 Hom.: 23786 Cov.: 34

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.423 AC: 11 AN: 26 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 6 AN XY: 18

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 8 AN: 16

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00280662), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.555 AC: 84422 AN: 152174 Hom.: 23814 Cov.: 34 AF XY: 0.553 AC XY: 41124 AN XY: 74392

African (AFR) AF: 0.570 AC: 23691 AN: 41536

American (AMR) AF: 0.612 AC: 9357 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4070 AN: 5176

South Asian (SAS) AF: 0.510 AC: 2461 AN: 4826

European-Finnish (FIN) AF: 0.475 AC: 5024 AN: 10566

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36862 AN: 67986

Other (OTH) AF: 0.539 AC: 1139 AN: 2114

Alfa AF: 0.549 Hom.: 2846

Bravo AF: 0.568

Asia WGS AF: 0.561 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.0070
Mutation Taster		=100/0	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: rs3785125; hg19: chr16-68388392;