chr12-121654342-C-A

Variant names:

• chr12-121654342-C-A
• rs782408547
• NM_173855.5:c.395G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173855.5(MORN3):​c.395G>T​(p.Ser132Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MORN3 NM_173855.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.196
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17619339).

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.395G>T	p.Ser132Ile	missense	Exon 3 of 6	NP_776254.3	Q6PF18-1
	MORN3	NM_001363685.2		c.395G>T	p.Ser132Ile	missense	Exon 4 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.395G>T	p.Ser132Ile	missense	Exon 3 of 6	ENSP00000347486.3	Q6PF18-1
	MORN3	ENST00000542364.1	TSL:1	n.395G>T		non_coding_transcript_exon	Exon 4 of 6	ENSP00000445643.1	Q6PF18-2
	MORN3	ENST00000879182.1		c.395G>T	p.Ser132Ile	missense	Exon 4 of 7	ENSP00000549241.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451296 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 720602

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 43064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25800

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 83962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107618

Other (OTH) AF: 0.00 AC: 0 AN: 60060

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	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.20
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.063
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.42	B
Vest4		0.32
MutPred		0.41		Loss of disorder (P = 0.041)
MVP		0.57
MPC		0.35
ClinPred		0.68	D
GERP RS		2.9
Varity_R		0.13
gMVP		0.39
Mutation Taster		=94/6	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: rs782408547; hg19: chr12-122092248;