chr9-120659383-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080497.3(MEGF9):​c.794C>T​(p.Pro265Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MEGF9
NM_001080497.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.016352683).
BP6
Variant 9-120659383-G-A is Benign according to our data. Variant chr9-120659383-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2320786.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEGF9NM_001080497.3 linkuse as main transcriptc.794C>T p.Pro265Leu missense_variant 2/6 ENST00000373930.4 NP_001073966.2 Q9H1U4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEGF9ENST00000373930.4 linkuse as main transcriptc.794C>T p.Pro265Leu missense_variant 2/62 NM_001080497.3 ENSP00000363040.3 Q9H1U4

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
151980
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248358
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134732
show subpopulations
Gnomad AFR exome
AF:
0.000259
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000890
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461268
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
726924
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
151980
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000990
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.0000414
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.5
DANN
Benign
0.26
DEOGEN2
Benign
0.0071
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0041
N
LIST_S2
Benign
0.040
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.016
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.8
N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
2.1
N
REVEL
Benign
0.057
Sift
Benign
1.0
T
Sift4G
Benign
0.76
T
Polyphen
0.0
B
Vest4
0.12
MVP
0.043
ClinPred
0.0050
T
GERP RS
1.7
Varity_R
0.025
gMVP
0.50

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368773739; hg19: chr9-123421661; API