NM_001271938.2:c.1197C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001271938.2(MEGF8):c.1197C>T(p.Pro399Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00941 in 1,607,412 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 86 hom. )

Consequence

MEGF8
NM_001271938.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -7.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 19-42336299-C-T is Benign according to our data. Variant chr19-42336299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00733 (1117/152360) while in subpopulation NFE AF= 0.0101 (688/68030). AF 95% confidence interval is 0.00949. There are 9 homozygotes in gnomad4. There are 598 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF8	NM_001271938.2 link	c.1197C>T	p.Pro399Pro	synonymous_variant	Exon 6 of 42	ENST00000251268.11	NP_001258867.1	Q7Z7M0-1
MEGF8	NM_001410.3 link	c.1197C>T	p.Pro399Pro	synonymous_variant	Exon 6 of 41		NP_001401.2	Q7Z7M0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MEGF8	ENST00000251268.11 link	c.1197C>T	p.Pro399Pro	synonymous_variant	Exon 6 of 42	5	NM_001271938.2	ENSP00000251268.5	Q7Z7M0-1
MEGF8	ENST00000334370.8 link	c.1197C>T	p.Pro399Pro	synonymous_variant	Exon 6 of 41	1		ENSP00000334219.4	Q7Z7M0-2
MEGF8	ENST00000378073 link	c.-5889C>T		5_prime_UTR_variant	Exon 6 of 41	5		ENSP00000367313.4	F5GZG7

Frequencies

GnomAD3 genomes

AF:

0.00734

AC:

1118

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00796

AC:

1939

AN:

243656

Hom.:

AF XY:

0.00836

AC XY:

1109

AN XY:

132648

show subpopulations

Gnomad AFR exome

AF:

0.00150

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00987

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00763

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.00939

Gnomad OTH exome

AF:

0.00787

GnomAD4 exome

AF:

0.00962

AC:

14002

AN:

1455052

Hom.:

Cov.:

AF XY:

0.00971

AC XY:

7032

AN XY:

723910

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00517

Gnomad4 ASJ exome

AF:

0.00975

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00800

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00848

GnomAD4 genome

AF:

0.00733

AC:

1117

AN:

152360

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

598

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00674

Hom.:

Bravo

AF:

0.00580

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0119

EpiControl

AF:

0.0103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 05, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MEGF8: BP4, BP7, BS1, BS2 -

MEGF8-related Carpenter syndrome

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.86

DANN

Benign

0.52

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