Variant 19-42368937-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001271938.2(MEGF8):c.6576G>A(p.Thr2192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,613,866 control chromosomes in the GnomAD database, including 279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 134 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 145 hom. )

Consequence

MEGF8
NM_001271938.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -8.17

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-42368937-G-A is Benign according to our data. Variant chr19-42368937-G-A is described in ClinVar as [Benign]. Clinvar id is 473339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF8	NM_001271938.2 linkuse as main transcript	c.6576G>A	p.Thr2192=	synonymous_variant	37/42	ENST00000251268.11	NP_001258867.1
MEGF8	NM_001410.3 linkuse as main transcript	c.6375G>A	p.Thr2125=	synonymous_variant	36/41		NP_001401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF8	ENST00000251268.11 linkuse as main transcript	c.6576G>A	p.Thr2192=	synonymous_variant	37/42	5	NM_001271938.2	ENSP00000251268	A2	Q7Z7M0-1
MEGF8	ENST00000334370.8 linkuse as main transcript	c.6375G>A	p.Thr2125=	synonymous_variant	36/41	1		ENSP00000334219	P2	Q7Z7M0-2
MEGF8	ENST00000378073.5 linkuse as main transcript	c.-510G>A		5_prime_UTR_variant	37/41	5		ENSP00000367313
MEGF8	ENST00000598762.1 linkuse as main transcript	c.161+6724G>A		intron_variant		3		ENSP00000471370

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3354

AN:

152198

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00610

AC:

1531

AN:

250902

Hom.:

AF XY:

0.00438

AC XY:

594

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000776

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00291

AC:

4248

AN:

1461550

Hom.:

145

Cov.:

AF XY:

0.00264

AC XY:

1916

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000487

Gnomad4 OTH exome

AF:

0.00742

GnomAD4 genome

AF:

0.0222

AC:

3388

AN:

152316

Hom.:

134

Cov.:

AF XY:

0.0216

AC XY:

1611

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MEGF8-related Carpenter syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.23

DANN

Benign

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over