Genetic Variant NM_178832.4:c.310G>A (chr10-97616394-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

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

GnomAD2 exomes

AF:

0.0000207

AC:

AN:

241376

AF XY:

0.0000153

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 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

African (AFR)

AF:

0.000182

AC:

AN:

33054

American (AMR)

AF:

0.00

AC:

AN:

42814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25668

East Asian (EAS)

AF:

0.00

AC:

AN:

39578

South Asian (SAS)

AF:

0.0000235

AC:

AN:

84988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1107938

Other (OTH)

AF:

0.0000167

AC:

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41490

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

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

PhyloP100

6.0

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

Mutation Taster

=39/61

disease causing

(source)

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

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NM_178832.4:c.310G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over