NM_178832.4:c.397C>T

Variant names:

• chr10-97616307-G-A
• rs147515528
• NM_178832.4:c.397C>T

Variant summary

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

The NM_178832.4(MORN4):​c.397C>T​(p.Arg133Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,612,056 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: MORN4 NM_178832.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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]

ENSG00000249967 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN4	NM_178832.4	c.397C>T	p.Arg133Trp	missense_variant	Exon 5 of 5	ENST00000307450.11	NP_849154.1
MORN4	NM_001098831.2	c.397C>T	p.Arg133Trp	missense_variant	Exon 5 of 5		NP_001092301.1
MORN4	XM_011539251.4	c.397C>T	p.Arg133Trp	missense_variant	Exon 5 of 5		XP_011537553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORN4	ENST00000307450.11	c.397C>T	p.Arg133Trp	missense_variant	Exon 5 of 5	1	NM_178832.4	ENSP00000307636.6
ENSG00000249967	ENST00000370649.3	c.345+14317G>A		intron_variant	Intron 2 of 9	2		ENSP00000359683.3
MORN4	ENST00000478953.1	c.*86C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000441070.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000124 AC: 31 AN: 249766 AF XY: 0.000126

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000879

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000281 AC: 410 AN: 1459878 Hom.: 0 Cov.: 30 AF XY: 0.000259 AC XY: 188 AN XY: 726156

African (AFR) AF: 0.0000599 AC: 2 AN: 33368

American (AMR) AF: 0.0000677 AC: 3 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.000358 AC: 398 AN: 1111114

Other (OTH) AF: 0.0000829 AC: 5 AN: 60296

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74328

African (AFR) AF: 0.000145 AC: 6 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.000178

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000546

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.397C>T (p.R133W) alteration is located in exon 5 (coding exon 4) of the MORN4 gene. This alteration results from a C to T substitution at nucleotide position 397, causing the arginine (R) at amino acid position 133 to be replaced by a tryptophan (W). 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	0.24
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.58
MVP		0.62
MPC		0.61
ClinPred		0.33	T
GERP RS		3.1
Varity_R		0.42
gMVP		0.68
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147515528; hg19: chr10-99376064;