Genetic Variant MORN4:p.Asp104Asn (chr10-97616394-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178832.4(MORN4):c.310G>A(p.Asp104Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,605,158 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MORN4
NM_178832.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Variant links:

Genes affected

MORN4 (HGNC:24001): (MORN repeat containing 4) Predicted to be involved in response to axon injury. Located in cytoplasm and filopodium tip. [provided by Alliance of Genome Resources, Apr 2022]

MORN4 links:

ENSG00000249967 (HGNC:):

ENSG00000249967 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28983623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN4	NM_178832.4 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 5 of 5	ENST00000307450.11	NP_849154.1	Q8NDC4-1A6XB87
MORN4	NM_001098831.2 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 5 of 5		NP_001092301.1	Q8NDC4-1A6XB87
MORN4	XM_011539251.4 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 5 of 5		XP_011537553.1	Q8NDC4-1A6XB87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MORN4	ENST00000307450.11 link	c.310G>A	p.Asp104Asn	missense_variant	Exon 5 of 5	1	NM_178832.4	ENSP00000307636.6	Q8NDC4-1
ENSG00000249967	ENST00000370649.3 link	c.345+14404C>T		intron_variant	Intron 2 of 9	2		ENSP00000359683.3	E9PAM4
MORN4	ENST00000478953.1 link	c.200G>A	p.Ter67Ter	stop_retained_variant	Exon 4 of 4	2		ENSP00000441070.1	G3V1L7

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

241376

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130736

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.0000310

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:

0.00000895

AC:

AN:

1453006

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

722260

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000655

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:

0.0000666

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>A (p.D104N) alteration is located in exon 5 (coding exon 4) of the MORN4 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the aspartic acid (D) at amino acid position 104 to be replaced by an asparagine (N). 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

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.027

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.40

Sift

Benign

0.042

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.53

MVP

0.77

MPC

0.68

ClinPred

0.74

GERP RS

5.0

Varity_R

0.44

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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