Genetic Variant NM_173855.5:c.406A>G (chr12-121654331-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173855.5(MORN3):c.406A>G(p.Ile136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MORN3
NM_173855.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.349

Publications

0 publications found

Variant links:

Genes affected

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

MORN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03206286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORN3	NM_173855.5	MANE Select	c.406A>G	p.Ile136Val	missense	Exon 3 of 6	NP_776254.3	Q6PF18-1
	MORN3	NM_001363685.2		c.406A>G	p.Ile136Val	missense	Exon 4 of 7	NP_001350614.1	Q6PF18-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MORN3	ENST00000355329.7	TSL:1 MANE Select	c.406A>G	p.Ile136Val	missense	Exon 3 of 6	ENSP00000347486.3	Q6PF18-1
MORN3	ENST00000542364.1	TSL:1	n.406A>G		non_coding_transcript_exon	Exon 4 of 6	ENSP00000445643.1	Q6PF18-2
MORN3	ENST00000879182.1		c.406A>G	p.Ile136Val	missense	Exon 4 of 7	ENSP00000549241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

229114

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720320

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33426

American (AMR)

AF:

0.0000233

AC:

AN:

42994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25784

East Asian (EAS)

AF:

0.00

AC:

AN:

39356

South Asian (SAS)

AF:

0.00

AC:

AN:

83898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107508

Other (OTH)

AF:

0.00

AC:

AN:

60040

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.011

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.0031

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.17

PhyloP100

0.35

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.22

REVEL

Benign

0.014

Sift

Benign

0.67

Sift4G

Benign

0.69

Polyphen

0.0030

Vest4

0.075

MutPred

0.31

Gain of disorder (P = 0.1631)

MVP

0.12

MPC

0.14

ClinPred

0.12

GERP RS

2.5

Varity_R

0.025

gMVP

0.28

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over