9-122169704-C-G

Variant names:

• chr9-122169704-C-G
• NM_198469.4:c.255C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198469.4(MORN5):​c.255C>G​(p.Asp85Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MORN5 NM_198469.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.440

Genes affected

MORN5 (HGNC:17841): (MORN repeat containing 5)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19403502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORN5	NM_198469.4	c.255C>G	p.Asp85Glu	missense_variant	Exon 3 of 5	ENST00000373764.8	NP_940871.2
MORN5	NM_001286828.2	c.195+2789C>G		intron_variant	Intron 2 of 3		NP_001273757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORN5	ENST00000373764.8	c.255C>G	p.Asp85Glu	missense_variant	Exon 3 of 5	1	NM_198469.4	ENSP00000362869.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.255C>G (p.D85E) alteration is located in exon 3 (coding exon 3) of the MORN5 gene. This alteration results from a C to G substitution at nucleotide position 255, causing the aspartic acid (D) at amino acid position 85 to be replaced by a glutamic acid (E). 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	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.31	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.22	B;.
Vest4		0.69
MutPred		0.38		Gain of loop (P = 0.1069);.;
MVP		0.014
MPC		0.25
ClinPred		0.77	D
GERP RS		-0.0095
Varity_R		0.092
gMVP		0.55

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-124931983;