rs28483598
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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
NM_001271938.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.524
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]
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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 | c.7053C>T | p.Cys2351= | synonymous_variant | 40/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.6852C>T | p.Cys2284= | synonymous_variant | 39/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.7053C>T | p.Cys2351= | synonymous_variant | 40/42 | 5 | NM_001271938.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0153 AC: 2307AN: 150332Hom.: 58 Cov.: 27
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GnomAD3 exomes AF: 0.00424 AC: 859AN: 202810Hom.: 15 AF XY: 0.00317 AC XY: 343AN XY: 108230
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GnomAD4 exome AF: 0.00215 AC: 3079AN: 1431118Hom.: 71 Cov.: 31 AF XY: 0.00197 AC XY: 1394AN XY: 708996
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GnomAD4 genome ? AF: 0.0154 AC: 2311AN: 150448Hom.: 59 Cov.: 27 AF XY: 0.0150 AC XY: 1099AN XY: 73348
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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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at