Variant 19-42370748-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001271938.2(MEGF8):c.7053C>T(p.Cys2351=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,581,566 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 59 hom., cov: 27)

Exomes 𝑓: 0.0022 ( 71 hom. )

Consequence

MEGF8
NM_001271938.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.524

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 19-42370748-C-T is Benign according to our data. Variant chr19-42370748-C-T is described in ClinVar as [Benign]. Clinvar id is 473342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.524 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF8	NM_001271938.2 linkuse as main transcript	c.7053C>T	p.Cys2351=	synonymous_variant	40/42	ENST00000251268.11
MEGF8	NM_001410.3 linkuse as main transcript	c.6852C>T	p.Cys2284=	synonymous_variant	39/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF8	ENST00000251268.11 linkuse as main transcript	c.7053C>T	p.Cys2351=	synonymous_variant	40/42	5	NM_001271938.2	A2	Q7Z7M0-1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2307

AN:

150332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00711

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000591

Gnomad OTH

AF:

0.0136

GnomAD3 exomes

AF:

0.00424

AC:

859

AN:

202810

Hom.:

AF XY:

0.00317

AC XY:

343

AN XY:

108230

show subpopulations

Gnomad AFR exome

AF:

0.0525

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.00164

Gnomad EAS exome

AF:

0.000134

Gnomad SAS exome

AF:

0.000278

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000738

Gnomad OTH exome

AF:

0.00416

GnomAD4 exome

AF:

0.00215

AC:

3079

AN:

1431118

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1394

AN XY:

708996

show subpopulations

Gnomad4 AFR exome

AF:

0.0605

Gnomad4 AMR exome

AF:

0.00384

Gnomad4 ASJ exome

AF:

0.00137

Gnomad4 EAS exome

AF:

0.0000523

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.000458

Gnomad4 OTH exome

AF:

0.00495

GnomAD4 genome

AF:

0.0154

AC:

2311

AN:

150448

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1099

AN XY:

73348

show subpopulations

Gnomad4 AFR

AF:

0.0517

Gnomad4 AMR

AF:

0.00710

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000591

Gnomad4 OTH

AF:

0.0134

Alfa

AF:

0.00728

Hom.:

Bravo

AF:

0.0176

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MEGF8-related Carpenter syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

3.5

DANN

Benign

0.93

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