12-121659214-A-G

Variant names:

• chr12-121659214-A-G
• rs1300178646
• NM_173855.5:c.280T>C

Variant summary

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

The NM_173855.5(MORN3):​c.280T>C​(p.Trp94Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W94G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MORN3 NM_173855.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

MORN3 (HGNC:29807): (MORN repeat containing 3) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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_173855.5. 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
	MORN3	NM_173855.5	MANE Select	c.280T>C	p.Trp94Arg	missense	Exon 2 of 6	NP_776254.3	Q6PF18-1
	MORN3	NM_001363685.2		c.280T>C	p.Trp94Arg	missense	Exon 3 of 7	NP_001350614.1	Q6PF18-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORN3	ENST00000355329.7	TSL:1 MANE Select	c.280T>C	p.Trp94Arg	missense	Exon 2 of 6	ENSP00000347486.3	Q6PF18-1
	MORN3	ENST00000542364.1	TSL:1	n.280T>C		non_coding_transcript_exon	Exon 3 of 6	ENSP00000445643.1	Q6PF18-2
	MORN3	ENST00000879182.1		c.280T>C	p.Trp94Arg	missense	Exon 3 of 7	ENSP00000549241.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.17	N
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Benign	0.21	T
Sift4G	Benign	0.66	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.46		Gain of disorder (P = 0.0045)
MVP		0.31
MPC		0.33
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.64
Mutation Taster		=87/13	polymorphism

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: rs1300178646; hg19: chr12-122097120; COSMIC: COSV62507106;