rs587779350
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000618.5(IGF1):c.292C>T(p.Arg98Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R98Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000618.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1 | NM_000618.5 | c.292C>T | p.Arg98Trp | missense_variant | 3/4 | ENST00000337514.11 | |
LINC02456 | XR_007063427.1 | n.6691-3452G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1 | ENST00000337514.11 | c.292C>T | p.Arg98Trp | missense_variant | 3/4 | 1 | NM_000618.5 | P1 | |
LINC02456 | ENST00000704346.1 | n.1067-3452G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461464Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727028
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Growth delay due to insulin-like growth factor type 1 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 14, 2022 | This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 127243). This missense change has been observed in individual(s) with primordial dwarfism and congenital microcephaly (PMID: 24389050, 30214071). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 98 of the IGF1 protein (p.Arg98Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at