chr6-75922133-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001563.4(IMPG1):c.2350G>A(p.Val784Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,410,134 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001563.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IMPG1 | NM_001563.4 | c.2350G>A | p.Val784Ile | missense_variant | 17/17 | ENST00000369950.8 | |
IMPG1 | NM_001282368.2 | c.2116G>A | p.Val706Ile | missense_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IMPG1 | ENST00000369950.8 | c.2350G>A | p.Val784Ile | missense_variant | 17/17 | 1 | NM_001563.4 | P2 | |
IMPG1 | ENST00000611179.4 | c.2116G>A | p.Val706Ile | missense_variant | 16/16 | 5 | A2 | ||
IMPG1 | ENST00000369952.3 | c.433G>A | p.Val145Ile | missense_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000808 AC: 17AN: 210434Hom.: 0 AF XY: 0.0000711 AC XY: 8AN XY: 112588
GnomAD4 exome AF: 0.0000700 AC: 88AN: 1257934Hom.: 0 Cov.: 19 AF XY: 0.0000680 AC XY: 43AN XY: 632242
GnomAD4 genome AF: 0.000105 AC: 16AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74426
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 784 of the IMPG1 protein (p.Val784Ile). This variant is present in population databases (rs576579238, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with IMPG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 946530). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2021 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at