Variant rs35473255 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.4020C>T(p.Tyr1340Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,612,110 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 219 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 215 hom. )

Consequence

MEGF8
NM_001271938.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

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=-0.52).

BP6

Variant 19-42354596-C-T is Benign according to our data. Variant chr19-42354596-C-T is described in ClinVar as [Benign]. Clinvar id is 473330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.4020C>T	p.Tyr1340Tyr	synonymous_variant	23/42	ENST00000251268.11	NP_001258867.1	Q7Z7M0-1
MEGF8	NM_001410.3 linkuse as main transcript	c.3819C>T	p.Tyr1273Tyr	synonymous_variant	22/41		NP_001401.2	Q7Z7M0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEGF8	ENST00000251268.11 linkuse as main transcript	c.4020C>T	p.Tyr1340Tyr	synonymous_variant	23/42	5	NM_001271938.2	ENSP00000251268.5	Q7Z7M0-1
MEGF8	ENST00000334370.8 linkuse as main transcript	c.3819C>T	p.Tyr1273Tyr	synonymous_variant	22/41	1		ENSP00000334219.4	Q7Z7M0-2
MEGF8	ENST00000378073.5 linkuse as main transcript	c.-3066C>T		5_prime_UTR_premature_start_codon_gain_variant	23/41	5		ENSP00000367313.4	F5GZG7
MEGF8	ENST00000378073.5 linkuse as main transcript	c.-3066C>T		5_prime_UTR_variant	23/41	5		ENSP00000367313.4	F5GZG7

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4639

AN:

152176

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00442

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00897

AC:

2243

AN:

250084

Hom.:

AF XY:

0.00686

AC XY:

927

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.00664

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00424

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000672

Gnomad OTH exome

AF:

0.00640

GnomAD4 exome

AF:

0.00344

AC:

5025

AN:

1459816

Hom.:

215

Cov.:

AF XY:

0.00294

AC XY:

2132

AN XY:

726032

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.00746

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.000418

Gnomad4 FIN exome

AF:

0.0000949

Gnomad4 NFE exome

AF:

0.000375

Gnomad4 OTH exome

AF:

0.00852

GnomAD4 genome

AF:

0.0305

AC:

4642

AN:

152294

Hom.:

219

Cov.:

AF XY:

0.0295

AC XY:

2194

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00443

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0346

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00130

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 16, 2019	- -

MEGF8-related Carpenter syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.6

DANN

Benign

0.58

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