chr18-62090521-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM5BP4_StrongBP6_Very_StrongBS2
The NM_176787.5(PIGN):āc.2238A>Gā(p.Ile746Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,611,218 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I746R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_176787.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2238A>G | p.Ile746Met | missense_variant | 24/31 | ENST00000640252.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.2238A>G | p.Ile746Met | missense_variant | 24/31 | 1 | NM_176787.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00113 AC: 172AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00135 AC: 333AN: 247046Hom.: 0 AF XY: 0.00144 AC XY: 193AN XY: 134068
GnomAD4 exome AF: 0.00120 AC: 1754AN: 1458906Hom.: 5 Cov.: 28 AF XY: 0.00124 AC XY: 901AN XY: 725768
GnomAD4 genome AF: 0.00113 AC: 172AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87AN XY: 74480
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 26, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at