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GeneBe

21-36360030-A-G

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.Gln428=) 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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.828 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MORC3NM_015358.3 linkuse as main transcriptc.1284A>G p.Gln428= synonymous_variant 11/17 ENST00000400485.6
MORC3NM_001320445.2 linkuse as main transcriptc.1071A>G p.Gln357= synonymous_variant 10/16
MORC3NM_001320446.2 linkuse as main transcriptc.1071A>G p.Gln357= synonymous_variant 12/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MORC3ENST00000400485.6 linkuse as main transcriptc.1284A>G p.Gln428= synonymous_variant 11/171 NM_015358.3 P1
MORC3ENST00000485299.1 linkuse as main transcriptn.668A>G non_coding_transcript_exon_variant 4/43
MORC3ENST00000487909.5 linkuse as main transcriptn.1245A>G non_coding_transcript_exon_variant 10/162

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00275
AC:
418
AN:
152200
Hom.:
2
Cov.:
32
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.:
7
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.:
27
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00274
AC:
418
AN:
152318
Hom.:
2
Cov.:
32
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.:
1
Bravo
AF:
0.00269
Asia WGS
AF:
0.00202
AC:
7
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023MORC3: 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.

Other links and lift over

dbSNP: rs192090360; hg19: chr21-37732328; COSMIC: COSV68203747; COSMIC: COSV68203747; API