NM_176787.5:c.2486C>T
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_176787.5(PIGN):c.2486C>T(p.Ala829Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,551,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A829T) has been classified as Uncertain significance.
Frequency
Consequence
NM_176787.5 missense
Scores
Clinical Significance
Conservation
Publications
- multiple congenital anomalies-hypotonia-seizures syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen, PanelApp Australia
- Fryns syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGN | NM_176787.5 | c.2486C>T | p.Ala829Val | missense_variant | Exon 27 of 31 | ENST00000640252.2 | NP_789744.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGN | ENST00000640252.2 | c.2486C>T | p.Ala829Val | missense_variant | Exon 27 of 31 | 1 | NM_176787.5 | ENSP00000492233.1 | ||
PIGN | ENST00000400334.7 | c.2486C>T | p.Ala829Val | missense_variant | Exon 26 of 30 | 1 | ENSP00000383188.2 | |||
PIGN | ENST00000638424.1 | n.*454C>T | non_coding_transcript_exon_variant | Exon 25 of 29 | 5 | ENSP00000491963.1 | ||||
PIGN | ENST00000638424.1 | n.*454C>T | 3_prime_UTR_variant | Exon 25 of 29 | 5 | ENSP00000491963.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000234 AC: 4AN: 171222 AF XY: 0.0000444 show subpopulations
GnomAD4 exome AF: 0.0000193 AC: 27AN: 1399054Hom.: 0 Cov.: 27 AF XY: 0.0000246 AC XY: 17AN XY: 691220 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74268 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.2486C>T (p.A829V) alteration is located in exon 27 (coding exon 24) of the PIGN gene. This alteration results from a C to T substitution at nucleotide position 2486, causing the alanine (A) at amino acid position 829 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 829 of the PIGN protein (p.Ala829Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PIGN-related conditions. ClinVar contains an entry for this variant (Variation ID: 586230). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at