chr17-1875679-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_002945.5(RPA1):c.473C>T(p.Ala158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A158T) has been classified as Uncertain significance.
Frequency
Consequence
NM_002945.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPA1 | NM_002945.5 | c.473C>T | p.Ala158Val | missense_variant | 7/17 | ENST00000254719.10 | |
RPA1 | NM_001355120.2 | c.434C>T | p.Ala145Val | missense_variant | 7/17 | ||
RPA1 | NM_001355121.2 | c.473C>T | p.Ala158Val | missense_variant | 7/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPA1 | ENST00000254719.10 | c.473C>T | p.Ala158Val | missense_variant | 7/17 | 1 | NM_002945.5 | P1 | |
RPA1 | ENST00000570451.5 | c.434C>T | p.Ala145Val | missense_variant | 7/7 | 3 | |||
RPA1 | ENST00000573924.1 | n.197C>T | non_coding_transcript_exon_variant | 3/6 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251296Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135830
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461740Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727170
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.473C>T (p.A158V) alteration is located in exon 7 (coding exon 7) of the RPA1 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a valine (V). 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