10-97619604-C-T

Variant names:

• chr10-97619604-C-T
• rs375012522
• NM_178832.4:c.50G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_178832.4(MORN4):​c.50G>A​(p.Arg17His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,634 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000093 (2 hom.)
• Consequence: MORN4 NM_178832.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN4	NM_178832.4	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 5	ENST00000307450.11	NP_849154.1
MORN4	NM_001098831.2	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 5		NP_001092301.1
MORN4	XM_011539251.4	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 5		XP_011537553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORN4	ENST00000307450.11	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 5	1	NM_178832.4	ENSP00000307636.6
MORN4	ENST00000370635.3	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 2	1		ENSP00000359669.3
ENSG00000249967	ENST00000370649.3	c.345+17614C>T		intron_variant	Intron 2 of 9	2		ENSP00000359683.3
MORN4	ENST00000478953.1	c.50G>A	p.Arg17His	missense_variant	Exon 2 of 4	2		ENSP00000441070.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152118 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000155 AC: 39 AN: 251472 Hom.: 1 AF XY: 0.000184 AC XY: 25 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000931 AC: 136 AN: 1461516 Hom.: 2 Cov.: 30 AF XY: 0.000125 AC XY: 91 AN XY: 727078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152118 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74282

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000814 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000123 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50G>A (p.R17H) alteration is located in exon 2 (coding exon 1) of the MORN4 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the arginine (R) at amino acid position 17 to be replaced by a histidine (H). 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	0.075
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.016	T;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.0071
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.099	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.70	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.21	T;T;D
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.15
MutPred		0.41		Gain of ubiquitination at K21 (P = 0.0482);Gain of ubiquitination at K21 (P = 0.0482);Gain of ubiquitination at K21 (P = 0.0482);
MVP		0.49
MPC		0.78
ClinPred		0.097	T
GERP RS		4.3
Varity_R		0.062
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -17

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

Publications

LitVar

Other links and lift over

dbSNP: rs375012522; hg19: chr10-99379361; COSMIC: COSV56729870;