Variant 1-2336818-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024848.3(MORN1):c.1069T>C(p.Cys357Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,596,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

MORN1
NM_024848.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.98

Variant links:

Genes affected

MORN1 (HGNC:25852): (MORN repeat containing 1)

MORN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.00845781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORN1	NM_024848.3 linkuse as main transcript	c.1069T>C	p.Cys357Arg	missense_variant	11/14	ENST00000378531.8	NP_079124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORN1	ENST00000378531.8 linkuse as main transcript	c.1069T>C	p.Cys357Arg	missense_variant	11/14	2	NM_024848.3	ENSP00000367792	P2	Q5T089-1
MORN1	ENST00000606372.5 linkuse as main transcript	n.1151T>C		non_coding_transcript_exon_variant	10/12	1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000284

AC:

AN:

229040

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

125116

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000326

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.000347

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000379

AC:

547

AN:

1443872

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

273

AN XY:

717596

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.000413

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.000309

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000297

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

Jun 01, 2023

The c.1069T>C (p.C357R) alteration is located in exon 11 (coding exon 11) of the MORN1 gene. This alteration results from a T to C substitution at nucleotide position 1069, causing the cysteine (C) at amino acid position 357 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.32

DANN

Benign

0.18

DEOGEN2

Benign

0.040

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.29

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0085

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

REVEL

Benign

0.044

Sift

Benign

0.54

Sift4G

Benign

0.52

Polyphen

0.0030

Vest4

0.13

MVP

0.17

MPC

0.030

ClinPred

0.026

GERP RS

-3.4

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

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