rs387906539
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_000208.4(INSR):āc.698T>Gā(p.Leu233Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_000208.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.698T>G | p.Leu233Arg | missense_variant | 3/22 | ENST00000302850.10 | |
INSR | NM_001079817.3 | c.698T>G | p.Leu233Arg | missense_variant | 3/21 | ||
INSR | XM_011527988.3 | c.698T>G | p.Leu233Arg | missense_variant | 3/22 | ||
INSR | XM_011527989.4 | c.698T>G | p.Leu233Arg | missense_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.698T>G | p.Leu233Arg | missense_variant | 3/22 | 1 | NM_000208.4 | A2 | |
INSR | ENST00000341500.9 | c.698T>G | p.Leu233Arg | missense_variant | 3/21 | 1 | P3 | ||
INSR | ENST00000598216.1 | n.673T>G | non_coding_transcript_exon_variant | 3/10 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461506Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727062
GnomAD4 genome ? Cov.: 30
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The INSR p.Leu233Arg variant was not identified in the literature nor was it identified in dbSNP, ClinVar, LOVD 3.0 or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). The p.Leu233 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.