rs9333554
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006502.3(POLH):āc.1751T>Cā(p.Leu584Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,614,212 control chromosomes in the GnomAD database, including 86 homozygotes. 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 Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L584L) has been classified as Likely benign.
Frequency
Consequence
NM_006502.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLH | NM_006502.3 | c.1751T>C | p.Leu584Pro | missense_variant | 11/11 | ENST00000372236.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLH | ENST00000372236.9 | c.1751T>C | p.Leu584Pro | missense_variant | 11/11 | 1 | NM_006502.3 | P1 | |
POLH | ENST00000372226.1 | c.*435T>C | 3_prime_UTR_variant | 11/11 | 1 | ||||
GTPBP2 | ENST00000496137.5 | c.*131+5953A>G | intron_variant, NMD_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0126 AC: 1917AN: 152206Hom.: 43 Cov.: 32
GnomAD3 exomes AF: 0.00342 AC: 860AN: 251426Hom.: 20 AF XY: 0.00239 AC XY: 325AN XY: 135902
GnomAD4 exome AF: 0.00134 AC: 1961AN: 1461888Hom.: 43 Cov.: 32 AF XY: 0.00109 AC XY: 793AN XY: 727244
GnomAD4 genome ? AF: 0.0126 AC: 1916AN: 152324Hom.: 43 Cov.: 32 AF XY: 0.0123 AC XY: 913AN XY: 74498
ClinVar
Submissions by phenotype
Xeroderma pigmentosum variant type Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at