Variant chr21-36360030-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015358.3(MORC3):c.1284A>G(p.Gln428Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,614,186 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 27 hom. )

Consequence

MORC3
NM_015358.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.828

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 21-36360030-A-G is Benign according to our data. Variant chr21-36360030-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2652646.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.828 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC3	NM_015358.3 link	c.1284A>G	p.Gln428Gln	synonymous_variant	11/17	ENST00000400485.6	NP_056173.1	Q14149Q4VBZ9
MORC3	NM_001320445.2 link	c.1071A>G	p.Gln357Gln	synonymous_variant	10/16		NP_001307374.1	B4DHJ4
MORC3	NM_001320446.2 link	c.1071A>G	p.Gln357Gln	synonymous_variant	12/18		NP_001307375.1	B4DHJ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MORC3	ENST00000400485.6 link	c.1284A>G	p.Gln428Gln	synonymous_variant	11/17	1	NM_015358.3	ENSP00000383333.1	Q14149
MORC3	ENST00000485299.1 link	n.668A>G		non_coding_transcript_exon_variant	4/4	3
MORC3	ENST00000487909.5 link	n.1245A>G		non_coding_transcript_exon_variant	10/16	2

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00445

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00343

AC:

855

AN:

249466

Hom.:

AF XY:

0.00386

AC XY:

523

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.00596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00420

AC:

6134

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

3191

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00457

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00274

AC:

418

AN:

152318

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

189

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00662

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00445

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.00269

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

MORC3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

DANN

Benign

0.49

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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

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