17-8143436-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002616.3(PER1):c.2902C>T(p.Arg968Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,612,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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. R968H) has been classified as Likely benign.
Frequency
Consequence
NM_002616.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PER1 | NM_002616.3 | c.2902C>T | p.Arg968Cys | missense_variant | 19/23 | ENST00000317276.9 | NP_002607.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PER1 | ENST00000317276.9 | c.2902C>T | p.Arg968Cys | missense_variant | 19/23 | 1 | NM_002616.3 | ENSP00000314420 | P1 | |
PER1 | ENST00000581082.5 | c.2833C>T | p.Arg945Cys | missense_variant | 18/22 | 5 | ENSP00000462064 | |||
PER1 | ENST00000582719.5 | c.2462-601C>T | intron_variant, NMD_transcript_variant | 5 | ENSP00000463054 | |||||
PER1 | ENST00000578089.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000606 AC: 15AN: 247546Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134134
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460030Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 726212
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.2902C>T (p.R968C) alteration is located in exon 19 (coding exon 18) of the PER1 gene. This alteration results from a C to T substitution at nucleotide position 2902, causing the arginine (R) at amino acid position 968 to be replaced by a cysteine (C). 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