dbSNP rs375012522: MORN4:p.Arg17Leu (chr10-97619604-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178832.4(MORN4):c.50G>T(p.Arg17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MORN4
NM_178832.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

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: Uncertain_significance. The variant received 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
MORN4	NM_178832.4 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 5	ENST00000307450.11	NP_849154.1	Q8NDC4-1A6XB87
MORN4	NM_001098831.2 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 5		NP_001092301.1	Q8NDC4-1A6XB87
MORN4	XM_011539251.4 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 5		XP_011537553.1	Q8NDC4-1A6XB87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MORN4	ENST00000307450.11 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 5	1	NM_178832.4	ENSP00000307636.6	Q8NDC4-1
MORN4	ENST00000370635.3 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 2	1		ENSP00000359669.3	Q8WVZ3
ENSG00000249967	ENST00000370649.3 link	c.345+17614C>A		intron_variant	Intron 2 of 9	2		ENSP00000359683.3	E9PAM4
MORN4	ENST00000478953.1 link	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 4	2		ENSP00000441070.1	G3V1L7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111662

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.041

T;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.0057

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.52

N;.;.

PhyloP100

2.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

N;N;D

REVEL

Benign

0.083

Sift

Benign

0.32

T;T;D

Sift4G

Benign

0.82

T;T;T

Polyphen

0.042

B;.;.

Vest4

0.45

MutPred

0.42

Gain of ubiquitination at K21 (P = 0.0556);Gain of ubiquitination at K21 (P = 0.0556);Gain of ubiquitination at K21 (P = 0.0556);

MVP

0.51

MPC

0.60

ClinPred

0.69

GERP RS

4.3

Varity_R

0.13

gMVP

0.36

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.23

Position offset: -17

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

Publications

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rs375012522

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over