12-121653254-C-T

Variant summary

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

The NM_173855.5(MORN3):​c.469G>A​(p.Gly157Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

MORN3
NM_173855.5 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
Variant links:
Genes affected
MORN3 (HGNC:29807): (MORN repeat containing 3) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 rank MANE Protein UniProt
MORN3NM_173855.5 linkc.469G>A p.Gly157Arg missense_variant Exon 4 of 6 ENST00000355329.7 NP_776254.3 Q6PF18-1
MORN3NM_001363685.2 linkc.469G>A p.Gly157Arg missense_variant Exon 5 of 7 NP_001350614.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MORN3ENST00000355329.7 linkc.469G>A p.Gly157Arg missense_variant Exon 4 of 6 1 NM_173855.5 ENSP00000347486.3 Q6PF18-1
MORN3ENST00000542364.1 linkn.464-446G>A intron_variant Intron 4 of 5 1 ENSP00000445643.1 Q6PF18-2
MORN3ENST00000392462.6 linkn.464-446G>A intron_variant Intron 3 of 4 3 ENSP00000376255.2 Q6PF18-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152154
Hom.:
0
Cov.:
32
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250520
Hom.:
0
AF XY:
0.0000812
AC XY:
11
AN XY:
135448
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461426
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000302
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74450
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.469G>A (p.G157R) alteration is located in exon 4 (coding exon 4) of the MORN3 gene. This alteration results from a G to A substitution at nucleotide position 469, causing the glycine (G) at amino acid position 157 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
0.17
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T
Eigen
Benign
0.0035
Eigen_PC
Benign
0.047
FATHMM_MKL
Benign
0.76
D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.35
T
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.40
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.026
D
Polyphen
0.14
B
Vest4
0.45
MutPred
0.89
Gain of solvent accessibility (P = 0.0171);
MVP
0.81
MPC
0.33
ClinPred
0.41
T
GERP RS
3.2
Varity_R
0.26
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.24
Position offset: -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.

Other links and lift over

dbSNP: rs543187775; hg19: chr12-122091160; COSMIC: COSV62506965; API