Variant 21-36320283-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015358.3(MORC3):c.19C>G(p.Arg7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,424,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MORC3
NM_015358.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

MORC3 (HGNC:23572): (MORC family CW-type zinc finger 3) This gene encodes a protein that localizes to the nuclear matrix and forms nuclear bodies via an ATP-dependent mechanism. The protein is predicted to have coiled-coil and zinc finger domains and has RNA binding activity. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2016]

MORC3 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06565678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MORC3	NM_015358.3 linkuse as main transcript	c.19C>G	p.Arg7Gly	missense_variant	1/17	ENST00000400485.6
MORC3	NM_001320445.2 linkuse as main transcript	c.-122C>G		5_prime_UTR_variant	1/16
MORC3	NM_001320446.2 linkuse as main transcript	c.-281C>G		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MORC3	ENST00000400485.6 linkuse as main transcript	c.19C>G	p.Arg7Gly	missense_variant	1/17	1	NM_015358.3	P1
MORC3	ENST00000492336.5 linkuse as main transcript	n.95C>G		non_coding_transcript_exon_variant	1/5	1
	ENST00000608391.1 linkuse as main transcript	n.388G>C		non_coding_transcript_exon_variant	1/1
MORC3	ENST00000487909.5 linkuse as main transcript	n.53C>G		non_coding_transcript_exon_variant	1/16	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

188566

Hom.:

AF XY:

0.0000290

AC XY:

AN XY:

103356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000211

AC:

AN:

1424194

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

706238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000256

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000455

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.19C>G (p.R7G) alteration is located in exon 1 (coding exon 1) of the MORC3 gene. This alteration results from a C to G substitution at nucleotide position 19, causing the arginine (R) at amino acid position 7 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.072

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

M_CAP

Benign

0.024

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.36

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.47

REVEL

Benign

0.018

Sift

Benign

0.66

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.12

MutPred

0.30

Gain of catalytic residue at R7 (P = 0.0847);

MVP

0.21

MPC

1.3

ClinPred

0.064

GERP RS

2.3

Varity_R

0.083

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over