4-2128216-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_181808.4(POLN):c.1879A>G(p.Ile627Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,604,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_181808.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLN | NM_181808.4 | c.1879A>G | p.Ile627Val | missense_variant | 19/26 | ENST00000511885.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLN | ENST00000511885.6 | c.1879A>G | p.Ile627Val | missense_variant | 19/26 | 5 | NM_181808.4 | P1 | |
POLN | ENST00000382865.5 | c.1879A>G | p.Ile627Val | missense_variant | 17/24 | 1 | P1 | ||
POLN | ENST00000511098.1 | c.778A>G | p.Ile260Val | missense_variant | 12/19 | 1 | |||
POLN | ENST00000514858.5 | n.886A>G | non_coding_transcript_exon_variant | 10/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000320 AC: 8AN: 250014Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135068
GnomAD4 exome AF: 0.0000145 AC: 21AN: 1452522Hom.: 0 Cov.: 28 AF XY: 0.0000207 AC XY: 15AN XY: 723142
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74510
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.1879A>G (p.I627V) alteration is located in exon 17 (coding exon 17) of the POLN gene. This alteration results from a A to G substitution at nucleotide position 1879, causing the isoleucine (I) at amino acid position 627 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