8-42870022-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_030954.4(RNF170):āc.304T>Cā(p.Cys102Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,334 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_030954.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135836
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461334Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727022
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Spastic paraplegia 85, autosomal recessive Pathogenic:2
Same or different nucleotide change resulting in same amino acid change has been previously reported to be associated with RNF170 related disorder (PMID:31636353). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID: 31636353). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.959>=0.6, 3CNET: 0.975>=0.75). The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -
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Spastic paraplegia Pathogenic:1
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Autosomal dominant sensory ataxia 1 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at