chr9-122174613-T-C

Position:

• chr9-122174613-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198469.4(MORN5):​c.425T>C​(p.Phe142Ser) 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. 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: 3.97

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORN5	NM_198469.4	c.425T>C	p.Phe142Ser	missense_variant	4/5	ENST00000373764.8
MORN5	NM_001286828.2	c.*22T>C		3_prime_UTR_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORN5	ENST00000373764.8	c.425T>C	p.Phe142Ser	missense_variant	4/5	1	NM_198469.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.425T>C (p.F142S) alteration is located in exon 4 (coding exon 4) of the MORN5 gene. This alteration results from a T to C substitution at nucleotide position 425, causing the phenylalanine (F) at amino acid position 142 to be replaced by a serine (S). 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	0.86
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.20	T
Polyphen		0.76	P
Vest4		0.81
MutPred		0.55		Gain of disorder (P = 0.0083);
MVP		0.21
MPC		0.75
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.77
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs1829419891; hg19: chr9-124936892;