rs773783457

Variant names:

• chr12-121659309-T-A
• rs773783457
• NM_173855.5:c.185A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-121659309-T-A
• chr12-121659309-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173855.5(MORN3):​c.185A>T​(p.Tyr62Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y62C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MORN3 NM_173855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

Genes affected

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

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN3	NM_173855.5	c.185A>T	p.Tyr62Phe	missense_variant	Exon 2 of 6	ENST00000355329.7	NP_776254.3
MORN3	NM_001363685.2	c.185A>T	p.Tyr62Phe	missense_variant	Exon 3 of 7		NP_001350614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORN3	ENST00000355329.7	c.185A>T	p.Tyr62Phe	missense_variant	Exon 2 of 6	1	NM_173855.5	ENSP00000347486.3
MORN3	ENST00000542364.1	n.185A>T		non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000445643.1
MORN3	ENST00000392462.6	n.185A>T		non_coding_transcript_exon_variant	Exon 2 of 5	3		ENSP00000376255.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.5	D
REVEL	Pathogenic	0.77
Sift	Benign	0.048	D
Sift4G	Uncertain	0.048	D
Polyphen		0.95	P
Vest4		0.67
MutPred		0.85		Loss of ubiquitination at K67 (P = 0.0683);
MVP		0.69
MPC		0.55
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.57
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs773783457; hg19: chr12-122097215;