rs36027220
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_181503.3(EXOSC8):āc.815G>Cā(p.Ser272Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,595,800 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S272I) has been classified as Uncertain significance.
Frequency
Consequence
NM_181503.3 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 | UniProt |
---|---|---|---|---|---|---|---|
EXOSC8 | NM_181503.3 | c.815G>C | p.Ser272Thr | missense_variant | 11/11 | ENST00000389704.4 | |
SUPT20H | NM_001014286.3 | downstream_gene_variant | ENST00000350612.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXOSC8 | ENST00000389704.4 | c.815G>C | p.Ser272Thr | missense_variant | 11/11 | 1 | NM_181503.3 | P1 | |
SUPT20H | ENST00000350612.11 | downstream_gene_variant | 1 | NM_001014286.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00394 AC: 599AN: 152162Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00385 AC: 959AN: 248810Hom.: 2 AF XY: 0.00397 AC XY: 534AN XY: 134438
GnomAD4 exome AF: 0.00576 AC: 8309AN: 1443520Hom.: 36 Cov.: 27 AF XY: 0.00584 AC XY: 4197AN XY: 719112
GnomAD4 genome AF: 0.00393 AC: 599AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.00336 AC XY: 250AN XY: 74448
ClinVar
Submissions by phenotype
Pontocerebellar hypoplasia, type 1C Pathogenic:1Uncertain:2Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 24, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 03, 2014 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Uncertain significance, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 25, 2024 | - - |
not provided Pathogenic:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | EXOSC8: BS2 - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 07, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 06, 2020 | This variant is associated with the following publications: (PMID: 27127732, 24989451, 29431110, 30581635, 29758258, 29093021, 31664448, 31980526) - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at