8-144394005-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_013291.3(CPSF1):c.3893G>A(p.Arg1298His) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013291.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249946Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135452
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460474Hom.: 0 Cov.: 58 AF XY: 0.00000964 AC XY: 7AN XY: 726406
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: CPSF1 c.3893G>A (p.Arg1298His) results in a non-conservative amino acid change located in the Cleavage/polyadenylation specificity factor, A subunit, C-terminal domain (IPR004871) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249946 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3893G>A in individuals affected with Myopia 27 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at