9-122169753-G-C

Position:

• chr9-122169753-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198469.4(MORN5):​c.304G>C​(p.Ala102Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 3.69

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32797432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORN5	NM_198469.4	c.304G>C	p.Ala102Pro	missense_variant	3/5	ENST00000373764.8
MORN5	NM_001286828.2	c.195+2838G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORN5	ENST00000373764.8	c.304G>C	p.Ala102Pro	missense_variant	3/5	1	NM_198469.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

May 24, 2024

The c.304G>C (p.A102P) alteration is located in exon 3 (coding exon 3) of the MORN5 gene. This alteration results from a G to C substitution at nucleotide position 304, causing the alanine (A) at amino acid position 102 to be replaced by a proline (P). 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	Benign	0.14
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.19
Sift	Benign	0.040	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.40	B;.
Vest4		0.29
MutPred		0.50		Gain of catalytic residue at P101 (P = 0.0113);.;
MVP		0.24
MPC		0.21
ClinPred		0.97	D
GERP RS		2.6
Varity_R		0.51
gMVP		0.88

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: chr9-124932032;