9-120605377-T-C

Position:

• chr9-120605377-T-C

Variant summary

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

The NM_001080497.3(MEGF9):​c.1622A>G​(p.Tyr541Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEGF9 NM_001080497.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

Genes affected

MEGF9 (HGNC:3234): (multiple EGF like domains 9) Predicted to be involved in several processes, including animal organ morphogenesis; cell migration; and substrate adhesion-dependent cell spreading. Predicted to be integral component of membrane. Predicted to be active in basement membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF9	NM_001080497.3	c.1622A>G	p.Tyr541Cys	missense_variant	6/6	ENST00000373930.4	NP_001073966.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF9	ENST00000373930.4	c.1622A>G	p.Tyr541Cys	missense_variant	6/6	2	NM_001080497.3	ENSP00000363040.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 11, 2024

The c.1622A>G (p.Y541C) alteration is located in exon 6 (coding exon 6) of the MEGF9 gene. This alteration results from a A to G substitution at nucleotide position 1622, causing the tyrosine (Y) at amino acid position 541 to be replaced by a cysteine (C). 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	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.81
MVP		0.54
ClinPred		0.94	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.82

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: chr9-123367655;