16-68355790-G-A

Variant names:

• chr16-68355790-G-A
• rs61745807
• NM_019023.5:c.1718G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_019023.5(PRMT7):​c.1718G>A​(p.Ser573Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00137 in 1,611,668 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (18 hom.)
• Consequence: PRMT7 NM_019023.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.65
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056096017).
• BP6: Variant 16-68355790-G-A is Benign according to our data. Variant chr16-68355790-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00609 (928/152330) while in subpopulation AFR AF = 0.0207 (862/41574). AF 95% confidence interval is 0.0196. There are 10 homozygotes in GnomAd4. There are 439 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.1718G>A	p.Ser573Asn	missense	Exon 17 of 19	NP_061896.1
	PRMT7	NM_001351143.3		c.1718G>A	p.Ser573Asn	missense	Exon 17 of 20	NP_001338072.1
	PRMT7	NM_001351144.3		c.1721G>A	p.Ser574Asn	missense	Exon 17 of 19	NP_001338073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRMT7	ENST00000441236.3	TSL:1 MANE Select	c.1718G>A	p.Ser573Asn	missense	Exon 17 of 19	ENSP00000409324.2
	PRMT7	ENST00000567542.5	TSL:1	n.1842G>A		non_coding_transcript_exon	Exon 8 of 10
	PRMT7	ENST00000692632.1		c.1721G>A	p.Ser574Asn	missense	Exon 17 of 19	ENSP00000510669.1

Frequencies

GnomAD3 genomes AF: 0.00610 AC: 929 AN: 152212 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00186 AC: 460 AN: 246748 AF XY: 0.00140

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000331

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.000880 AC: 1284 AN: 1459338 Hom.: 18 Cov.: 29 AF XY: 0.000825 AC XY: 599 AN XY: 725982

African (AFR) AF: 0.0230 AC: 770 AN: 33438

American (AMR) AF: 0.00114 AC: 51 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39614

South Asian (SAS) AF: 0.0000930 AC: 8 AN: 86014

European-Finnish (FIN) AF: 0.0000765 AC: 4 AN: 52302

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5752

European-Non Finnish (NFE) AF: 0.000265 AC: 294 AN: 1111244

Other (OTH) AF: 0.00201 AC: 121 AN: 60282

GnomAD4 genome AF: 0.00609 AC: 928 AN: 152330 Hom.: 10 Cov.: 33 AF XY: 0.00589 AC XY: 439 AN XY: 74482

African (AFR) AF: 0.0207 AC: 862 AN: 41574

American (AMR) AF: 0.00170 AC: 26 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00457 Hom.: 5

Bravo AF: 0.00694

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0257 AC: 113

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00232 AC: 282

EpiCase AF: 0.000491

EpiControl AF: 0.000357

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.7
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.096
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.016	D
Polyphen		0.40	B
Vest4		0.32
MVP		0.36
MPC		0.25
ClinPred		0.026	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.62
Mutation Taster		=93/7	polymorphism

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: rs61745807; hg19: chr16-68389693;