rs150607375
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001271938.2(MEGF8):āc.5281C>Gā(p.Leu1761Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000583 in 1,611,558 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L1761L) has been classified as Likely benign.
Frequency
Consequence
NM_001271938.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.5281C>G | p.Leu1761Val | missense_variant | 30/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.5080C>G | p.Leu1694Val | missense_variant | 29/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.5281C>G | p.Leu1761Val | missense_variant | 30/42 | 5 | NM_001271938.2 | A2 | |
MEGF8 | ENST00000334370.8 | c.5080C>G | p.Leu1694Val | missense_variant | 29/41 | 1 | P2 | ||
MEGF8 | ENST00000378073.5 | c.-1805C>G | 5_prime_UTR_variant | 30/41 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000441 AC: 67AN: 151960Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000463 AC: 114AN: 246420Hom.: 0 AF XY: 0.000465 AC XY: 62AN XY: 133356
GnomAD4 exome AF: 0.000597 AC: 872AN: 1459598Hom.: 1 Cov.: 32 AF XY: 0.000637 AC XY: 462AN XY: 725806
GnomAD4 genome AF: 0.000441 AC: 67AN: 151960Hom.: 1 Cov.: 31 AF XY: 0.000418 AC XY: 31AN XY: 74216
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.5080C>G (p.L1694V) alteration is located in exon 29 (coding exon 29) of the MEGF8 gene. This alteration results from a C to G substitution at nucleotide position 5080, causing the leucine (L) at amino acid position 1694 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
MEGF8-related Carpenter syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at