rs397517161
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_005633.4(SOS1):āc.281T>Cā(p.Ile94Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,488 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I94V) has been classified as Likely benign.
Frequency
Consequence
NM_005633.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.281T>C | p.Ile94Thr | missense_variant | 3/23 | ENST00000402219.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.281T>C | p.Ile94Thr | missense_variant | 3/23 | 1 | NM_005633.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250998Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135672
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460424Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726602
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 25, 2011 | The Ile94Thr variant has not been previously reported in the literature or been identified in our laboratory in over 1,300 individuals. This residue is not cons erved across evolutionarily distinct species and computational analyses (PolyPhe n2, SIFT, AlignGVGD, MAPP) provide inconsistent predictions regarding the impact to the normal function of the protein. It should be noted that the sensitivity and specificity of these computational programs has not been determined by our l aboratory. - |
Noonan syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University Hospital Muenster | Dec 13, 2021 | ACMG categories: PM1,PM2,PP3 - |
Fibromatosis, gingival, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at