chr16-68324804-C-A

Position:

• chr16-68324804-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019023.5(PRMT7):​c.254C>A​(p.Ala85Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 6.07

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRMT7	NM_019023.5	c.254C>A	p.Ala85Glu	missense_variant	5/19	ENST00000441236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRMT7	ENST00000441236.3	c.254C>A	p.Ala85Glu	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

Short stature-brachydactyly-obesity-global developmental delay syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;.;T;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.3	.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.0	D;.;D;.
REVEL	Uncertain	0.49
Sift	Benign	0.11	T;.;D;.
Sift4G	Benign	0.14	T;T;D;D
Polyphen		0.99	.;.;D;D
Vest4		0.85, 0.84
MutPred		0.68		Loss of catalytic residue at D88 (P = 0.0899);Loss of catalytic residue at D88 (P = 0.0899);Loss of catalytic residue at D88 (P = 0.0899);Loss of catalytic residue at D88 (P = 0.0899);
MVP		0.89
MPC		0.62
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.56
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

LitVar

Other links and lift over

dbSNP: rs1243665152; hg19: chr16-68358707;