rs8058517

Variant names:

• chr16-68345957-C-T
• rs8058517
• NM_019023.5:c.1055+155C>T

Variant summary

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

The NM_019023.5(PRMT7):​c.1055+155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,110 control chromosomes in the GnomAD database, including 1,874 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 0.15 (1874 hom., cov: 32)
• Consequence: PRMT7 NM_019023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRMT7	NM_019023.5	c.1055+155C>T		intron_variant	Intron 10 of 18	ENST00000441236.3	NP_061896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRMT7	ENST00000441236.3	c.1055+155C>T		intron_variant	Intron 10 of 18	1	NM_019023.5	ENSP00000409324.2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22627 AN: 151992 Hom.: 1869 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.149 AC: 22659 AN: 152110 Hom.: 1874 Cov.: 32 AF XY: 0.151 AC XY: 11266 AN XY: 74368

African (AFR) AF: 0.216 AC: 8981 AN: 41490

American (AMR) AF: 0.104 AC: 1590 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3472

East Asian (EAS) AF: 0.0692 AC: 357 AN: 5158

South Asian (SAS) AF: 0.168 AC: 811 AN: 4814

European-Finnish (FIN) AF: 0.172 AC: 1813 AN: 10552

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.119 AC: 8071 AN: 68008

Other (OTH) AF: 0.139 AC: 294 AN: 2110

Alfa AF: 0.128 Hom.: 701

Bravo AF: 0.147

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs8058517; hg19: chr16-68379860;