chr21-36741767-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005069.6(SIM2):c.901C>T(p.Arg301Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R301Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005069.6 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 |
---|---|---|---|---|---|---|---|
SIM2 | NM_005069.6 | c.901C>T | p.Arg301Trp | missense_variant | 8/11 | ENST00000290399.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIM2 | ENST00000290399.11 | c.901C>T | p.Arg301Trp | missense_variant | 8/11 | 1 | NM_005069.6 | P1 | |
SIM2 | ENST00000431229.1 | c.715C>T | p.Arg239Trp | missense_variant | 7/10 | 1 | |||
SIM2 | ENST00000481185.1 | n.1514C>T | non_coding_transcript_exon_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247858Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134602
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460920Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 726746
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.901C>T (p.R301W) alteration is located in exon 8 (coding exon 8) of the SIM2 gene. This alteration results from a C to T substitution at nucleotide position 901, causing the arginine (R) at amino acid position 301 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at