chr6-75923658-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001563.4(IMPG1):c.2292G>T(p.Lys764Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,587,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Consequence
NM_001563.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMPG1 | NM_001563.4 | c.2292G>T | p.Lys764Asn | missense_variant | 16/17 | ENST00000369950.8 | |
IMPG1 | NM_001282368.2 | c.2058G>T | p.Lys686Asn | missense_variant | 15/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMPG1 | ENST00000369950.8 | c.2292G>T | p.Lys764Asn | missense_variant | 16/17 | 1 | NM_001563.4 | P2 | |
IMPG1 | ENST00000611179.4 | c.2058G>T | p.Lys686Asn | missense_variant | 15/16 | 5 | A2 | ||
IMPG1 | ENST00000369952.3 | c.375G>T | p.Lys125Asn | missense_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 244170Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 131926
GnomAD4 exome AF: 0.00000348 AC: 5AN: 1435588Hom.: 0 Cov.: 25 AF XY: 0.00000419 AC XY: 3AN XY: 715416
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74424
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 25, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1058155). This variant has not been reported in the literature in individuals affected with IMPG1-related conditions. This variant is present in population databases (rs529799646, gnomAD 0.03%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 764 of the IMPG1 protein (p.Lys764Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at