chr10-101580326-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001174084.2(POLL):c.1285G>A(p.Asp429Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,802 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D429D) has been classified as Likely benign.
Frequency
Consequence
NM_001174084.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLL | NM_001174084.2 | c.1285G>A | p.Asp429Asn | missense_variant | 8/9 | ENST00000370162.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLL | ENST00000370162.8 | c.1285G>A | p.Asp429Asn | missense_variant | 8/9 | 1 | NM_001174084.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251402Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727146
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.1285G>A (p.D429N) alteration is located in exon 8 (coding exon 7) of the POLL gene. This alteration results from a G to A substitution at nucleotide position 1285, causing the aspartic acid (D) at amino acid position 429 to be replaced by an asparagine (N). 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