chr16-68324786-C-T

Position:

• chr16-68324786-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_019023.5(PRMT7):​c.236C>T​(p.Ser79Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRMT7 NM_019023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT7	NM_019023.5	c.236C>T	p.Ser79Leu	missense_variant	5/19	ENST00000441236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT7	ENST00000441236.3	c.236C>T	p.Ser79Leu	missense_variant	5/19	1	NM_019023.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

PRMT7-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 12, 2023

The PRMT7 c.236C>T variant is predicted to result in the amino acid substitution p.Ser79Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	.;.;.;D;D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D;.;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Pathogenic	3.0	.;.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.1	D;D;.;D;.
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0010	D;D;.;D;.
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		1.0	.;.;.;D;D
Vest4		0.97
MutPred		0.77		Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);
MVP		0.94
MPC		0.70
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.79
gMVP		0.94

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-68358689;