Variant 3-109035448-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000232603.10(MORC1):c.1351T>G(p.Phe451Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 1,494,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MORC1
ENST00000232603.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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:

Genome browser will be placed here

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.1351T>G	p.Phe451Val	missense_variant	15/28	ENST00000232603.10	NP_055244.3	Q86VD1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC1	ENST00000232603.10 linkuse as main transcript	c.1351T>G	p.Phe451Val	missense_variant	15/28	1	NM_014429.4	ENSP00000232603.5		Q86VD1-1
MORC1	ENST00000483760.1 linkuse as main transcript	c.1351T>G	p.Phe451Val	missense_variant	15/27	2		ENSP00000417282.1		Q86VD1-2

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

146866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000786

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:

0.00321

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000584

AC:

AN:

188382

Hom.:

AF XY:

0.0000193

AC XY:

AN XY:

103650

show subpopulations

Gnomad AFR exome

AF:

0.000742

Gnomad AMR exome

AF:

0.0000556

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000126

AC:

AN:

1347548

Hom.:

Cov.:

AF XY:

0.00000745

AC XY:

AN XY:

670936

show subpopulations

Gnomad4 AFR exome

AF:

0.000441

Gnomad4 AMR exome

AF:

0.0000297

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:

9.68e-7

Gnomad4 OTH exome

AF:

0.0000356

GnomAD4 genome

AF:

0.000218

AC:

AN:

146972

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

AN XY:

71464

show subpopulations

Gnomad4 AFR

AF:

0.000784

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

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

Jul 27, 2021

The c.1351T>G (p.F451V) alteration is located in exon 15 (coding exon 15) of the MORC1 gene. This alteration results from a T to G substitution at nucleotide position 1351, causing the phenylalanine (F) at amino acid position 451 to be replaced by a valine (V). 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

Benign

-0.21

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

D;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.016

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.63

MVP

0.42

MPC

0.83

ClinPred

0.55

GERP RS

4.7

Varity_R

0.53

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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