16-68349144-G-C

Variant names:

• chr16-68349144-G-C
• rs7197653
• NM_019023.5:c.1413+713G>C

Variant summary

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

The NM_019023.5(PRMT7):​c.1413+713G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,018 control chromosomes in the GnomAD database, including 3,327 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 0.19 (3327 hom., cov: 31)
• Consequence: PRMT7 NM_019023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 19 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 = 0.304 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.1413+713G>C		intron	N/A	NP_061896.1
	PRMT7	NM_001351143.3		c.1413+713G>C		intron	N/A	NP_001338072.1
	PRMT7	NM_001351144.3		c.1413+713G>C		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.1413+713G>C		intron	N/A	ENSP00000409324.2
	PRMT7	ENST00000567542.5	TSL:1	n.1537+2864G>C		intron	N/A
	PRMT7	ENST00000692632.1		c.1413+713G>C		intron	N/A	ENSP00000510669.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29110 AN: 151900 Hom.: 3313 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.192 AC: 29168 AN: 152018 Hom.: 3327 Cov.: 31 AF XY: 0.192 AC XY: 14288 AN XY: 74294

African (AFR) AF: 0.309 AC: 12791 AN: 41438

American (AMR) AF: 0.140 AC: 2138 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3468

East Asian (EAS) AF: 0.0663 AC: 343 AN: 5172

South Asian (SAS) AF: 0.179 AC: 859 AN: 4808

European-Finnish (FIN) AF: 0.172 AC: 1813 AN: 10562

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9988 AN: 67968

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.0730 Hom.: 85

Bravo AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		0.042
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: rs7197653; hg19: chr16-68383047;