10-97619604-C-A

Variant names:

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178832.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORN4	NM_178832.4	MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 2 of 5	NP_849154.1	Q8NDC4-1
	MORN4	NM_001098831.2		c.50G>T	p.Arg17Leu	missense	Exon 2 of 5	NP_001092301.1	Q8NDC4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORN4	ENST00000307450.11	TSL:1 MANE Select	c.50G>T	p.Arg17Leu	missense	Exon 2 of 5	ENSP00000307636.6	Q8NDC4-1
	MORN4	ENST00000370635.3	TSL:1	c.50G>T	p.Arg17Leu	missense	Exon 2 of 2	ENSP00000359669.3	Q8WVZ3
	ENSG00000249967	ENST00000370649.3	TSL:2	c.345+17614C>A		intron	N/A	ENSP00000359683.3	E9PAM4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461516 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727078

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111662

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0057
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N
PhyloP100		2.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.083
Sift	Benign	0.32	T
Sift4G	Benign	0.82	T
Polyphen		0.042	B
Vest4		0.45
MutPred		0.42		Gain of ubiquitination at K21 (P = 0.0556)
MVP		0.51
MPC		0.60
ClinPred		0.69	D
GERP RS		4.3
Varity_R		0.13
gMVP		0.36
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs375012522; hg19: chr10-99379361;