Variant 21-36337829-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015358.3(MORC3):c.343G>T(p.Ala115Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MORC3
NM_015358.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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 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, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MORC3	NM_015358.3 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	4/17	ENST00000400485.6	NP_056173.1
MORC3	NM_001320445.2 linkuse as main transcript	c.130G>T	p.Ala44Ser	missense_variant	3/16		NP_001307374.1
MORC3	NM_001320446.2 linkuse as main transcript	c.130G>T	p.Ala44Ser	missense_variant	5/18		NP_001307375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MORC3	ENST00000400485.6 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	4/17	1	NM_015358.3	ENSP00000383333	P1
MORC3	ENST00000492336.5 linkuse as main transcript	n.419G>T		non_coding_transcript_exon_variant	4/5	1
MORC3	ENST00000487909.5 linkuse as main transcript	n.304G>T		non_coding_transcript_exon_variant	3/16	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249540

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000248

AC:

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

Dec 19, 2022

The c.343G>T (p.A115S) alteration is located in exon 4 (coding exon 4) of the MORC3 gene. This alteration results from a G to T substitution at nucleotide position 343, causing the alanine (A) at amino acid position 115 to be replaced by a serine (S). 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

0.32

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.78

MetaSVM

Pathogenic

0.96

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.77

Sift

Benign

0.050

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.61

MutPred

0.52

Gain of disorder (P = 0.0198);

MVP

0.91

MPC

2.1

ClinPred

0.91

GERP RS

5.0

Varity_R

0.56

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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