chr16-68338420-C-G

Variant names:

• chr16-68338420-C-G
• rs3785114
• NM_019023.5:c.504+849C>G

Variant summary

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

The NM_019023.5(PRMT7):​c.504+849C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 151,614 control chromosomes in the GnomAD database, including 47,533 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 0.79 (47533 hom., cov: 28)
• Consequence: PRMT7 NM_019023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT7	NM_019023.5	c.504+849C>G		intron_variant	Intron 7 of 18	ENST00000441236.3	NP_061896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRMT7	ENST00000441236.3	c.504+849C>G		intron_variant	Intron 7 of 18	1	NM_019023.5	ENSP00000409324.2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 118931 AN: 151496 Hom.: 47464 Cov.: 28

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.785 AC: 119063 AN: 151614 Hom.: 47533 Cov.: 28 AF XY: 0.784 AC XY: 58063 AN XY: 74030

African (AFR) AF: 0.942 AC: 38948 AN: 41350

American (AMR) AF: 0.777 AC: 11833 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2238 AN: 3460

East Asian (EAS) AF: 0.854 AC: 4355 AN: 5100

South Asian (SAS) AF: 0.695 AC: 3337 AN: 4800

European-Finnish (FIN) AF: 0.722 AC: 7574 AN: 10484

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48350 AN: 67880

Other (OTH) AF: 0.758 AC: 1594 AN: 2104

Alfa AF: 0.658 Hom.: 1882

Bravo AF: 0.797

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.60
PhyloP100		0.23
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: rs3785114; hg19: chr16-68372323;