chr20-13221855-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_080826.2(ISM1):āc.79T>Cā(p.Ser27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,433,900 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (ā ).
Frequency
Consequence
NM_080826.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ISM1 | NM_080826.2 | c.79T>C | p.Ser27Pro | missense_variant | 1/6 | ENST00000262487.5 | NP_543016.1 | |
ISM1 | XM_017027680.2 | c.79T>C | p.Ser27Pro | missense_variant | 1/7 | XP_016883169.1 | ||
TASP1 | XR_001754319.3 | n.1369+94115A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ISM1 | ENST00000262487.5 | c.79T>C | p.Ser27Pro | missense_variant | 1/6 | 5 | NM_080826.2 | ENSP00000262487.3 |
Frequencies
GnomAD3 genomes AF: 0.0000922 AC: 14AN: 151902Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000331 AC: 2AN: 60350Hom.: 0 AF XY: 0.0000282 AC XY: 1AN XY: 35482
GnomAD4 exome AF: 0.000154 AC: 198AN: 1281888Hom.: 2 Cov.: 31 AF XY: 0.000141 AC XY: 89AN XY: 630928
GnomAD4 genome AF: 0.0000921 AC: 14AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2023 | The c.79T>C (p.S27P) alteration is located in exon 1 (coding exon 1) of the ISM1 gene. This alteration results from a T to C substitution at nucleotide position 79, causing the serine (S) at amino acid position 27 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
ISM1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 20, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at