Variant 3-108969671-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014429.4(MORC1):c.2602C>A(p.Gln868Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

MORC1
NM_014429.4 missense, splice_region

Scores

Splicing: ADA: 0.9720

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

MORC1 (HGNC:7198): (MORC family CW-type zinc finger 1) This gene encodes the human homolog of mouse morc and like the mouse protein it is testis-specific. Mouse studies support a testis-specific function since only male knockout mice are infertile; infertility is the only apparent defect. These studies further support a role for this protein early in spermatogenesis, possibly by affecting entry into apoptosis because testis from knockout mice show greatly increased numbers of apoptotic cells. [provided by RefSeq, Jan 2009]

MORC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC1	NM_014429.4 linkuse as main transcript	c.2602C>A	p.Gln868Lys	missense_variant, splice_region_variant	26/28	ENST00000232603.10	NP_055244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC1	ENST00000232603.10 linkuse as main transcript	c.2602C>A	p.Gln868Lys	missense_variant, splice_region_variant	26/28	1	NM_014429.4	ENSP00000232603	P2	Q86VD1-1
MORC1	ENST00000483760.1 linkuse as main transcript	c.2539C>A	p.Gln847Lys	missense_variant, splice_region_variant	25/27	2		ENSP00000417282	A2	Q86VD1-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251114

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135710

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000691

AC:

101

AN:

1460960

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000864

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Oct 20, 2023

The c.2602C>A (p.Q868K) alteration is located in exon 26 (coding exon 26) of the MORC1 gene. This alteration results from a C to A substitution at nucleotide position 2602, causing the glutamine (Q) at amino acid position 868 to be replaced by a lysine (K). 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

0.092

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.56

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.083

Sift

Benign

0.069

T;T

Sift4G

Uncertain

0.052

T;T

Polyphen

0.99

D;.

Vest4

0.36

MutPred

0.28

Gain of methylation at Q868 (P = 0.0023);.;

MVP

0.29

MPC

0.28

ClinPred

0.52

GERP RS

5.1

Varity_R

0.25

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.74

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