Genetic Variant NM_198469.4:c.151G>A (chr9-122166871-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198469.4(MORN5):c.151G>A(p.Gly51Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

MORN5
NM_198469.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.29

Variant links:

Genes affected

MORN5 (HGNC:17841): (MORN repeat containing 5)

MORN5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN5	NM_198469.4 link	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 5	ENST00000373764.8	NP_940871.2	Q5VZ52-1
MORN5	NM_001286828.2 link	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 4		NP_001273757.1	Q5VZ52A0A0A0MTF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MORN5	ENST00000373764.8 link	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 5	1	NM_198469.4	ENSP00000362869.3	Q5VZ52-1
MORN5	ENST00000536616.5 link	c.151G>A	p.Gly51Arg	missense_variant	Exon 2 of 4	1		ENSP00000437483.2	A0A0A0MTF6
MORN5	ENST00000418632.1 link	c.103G>A	p.Gly35Arg	missense_variant	Exon 2 of 4	5		ENSP00000409949.1	Q5T7S4
MORN5	ENST00000486801.1 link	n.104G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251170

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000924

AC:

135

AN:

1461758

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000638

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

.;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Pathogenic

0.84

MutationAssessor

Uncertain

2.9

.;M;.

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-7.6

D;D;D

REVEL

Pathogenic

0.77

Sift

Benign

0.033

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.81

MutPred

0.85

Loss of glycosylation at S50 (P = 0.048);Loss of glycosylation at S50 (P = 0.048);.;

MVP

0.67

MPC

0.63

ClinPred

0.92

GERP RS

4.8

Varity_R

0.73

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over