Variant 3-108984717-T-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.2323A>G(p.Ser775Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MORC1
ENST00000232603.10 missense, splice_region

Scores

Splicing: ADA: 0.9752

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.782

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.2323A>G	p.Ser775Gly	missense_variant, splice_region_variant	23/28	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.2323A>G	p.Ser775Gly	missense_variant, splice_region_variant	23/28	1	NM_014429.4	ENSP00000232603.5		Q86VD1-1
MORC1	ENST00000483760.1 linkuse as main transcript	c.2260A>G	p.Ser754Gly	missense_variant, splice_region_variant	22/27	2		ENSP00000417282.1		Q86VD1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

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:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 12, 2021

The c.2323A>G (p.S775G) alteration is located in exon 23 (coding exon 23) of the MORC1 gene. This alteration results from a A to G substitution at nucleotide position 2323, causing the serine (S) at amino acid position 775 to be replaced by a glycine (G). 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

0.071

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.51

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.43

T;T

Polyphen

0.99

D;.

Vest4

0.15

MutPred

0.15

Loss of disorder (P = 0.0562);.;

MVP

0.54

MPC

0.31

ClinPred

0.74

GERP RS

5.5

Varity_R

0.16

gMVP

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.91

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.29

Position offset: -1

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