chr19-42360810-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001271938.2(MEGF8):c.5524G>C(p.Val1842Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,603,882 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 2 hom. )

Consequence

MEGF8
NM_001271938.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31

Publications

1 publications found

Variant links:

Genes affected

MEGF8 (HGNC:3233): (multiple EGF like domains 8) The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

MEGF8 Gene-Disease associations (from GenCC):

MEGF8-related Carpenter syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
Carpenter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MEGF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059905946).

BP6

Variant 19-42360810-G-C is Benign according to our data. Variant chr19-42360810-G-C is described in ClinVar as Benign. ClinVar VariationId is 583365.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271938.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF8	NM_001271938.2	MANE Select	c.5524G>C	p.Val1842Leu	missense	Exon 32 of 42	NP_001258867.1
	MEGF8	NM_001410.3		c.5323G>C	p.Val1775Leu	missense	Exon 31 of 41	NP_001401.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MEGF8	ENST00000251268.11	TSL:5 MANE Select	c.5524G>C	p.Val1842Leu	missense	Exon 32 of 42	ENSP00000251268.5
MEGF8	ENST00000334370.8	TSL:1	c.5323G>C	p.Val1775Leu	missense	Exon 31 of 41	ENSP00000334219.4
MEGF8	ENST00000378073.5	TSL:5	c.-1562G>C		5_prime_UTR_premature_start_codon_gain	Exon 32 of 41	ENSP00000367313.4

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000723

AC:

164

AN:

226792

AF XY:

0.000661

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.000353

AC:

512

AN:

1451636

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

280

AN XY:

721396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33316

American (AMR)

AF:

0.0000468

AC:

AN:

42710

Ashkenazi Jewish (ASJ)

AF:

0.0142

AC:

368

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39322

South Asian (SAS)

AF:

0.00

AC:

AN:

84934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000686

AC:

AN:

1107530

Other (OTH)

AF:

0.00110

AC:

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000348

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68052

Other (OTH)

AF:

0.00143

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.000366

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000817

AC:

ExAC

AF:

0.000562

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MEGF8-related Carpenter syndrome

Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

M_CAP

Benign

0.025

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

1.3

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.3

REVEL

Benign

0.041

Sift

Benign

0.35

Sift4G

Uncertain

0.024

Polyphen

0.025

Vest4

0.28

MutPred

0.30

Loss of catalytic residue at V1842 (P = 0.0331)

MVP

0.22

MPC

0.032

ClinPred

0.016

GERP RS

3.2

PromoterAI

-0.0098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.14

gMVP

0.42

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over