NM_000553.6:c.4191G>C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000553.6(WRN):āc.4191G>Cā(p.Glu1397Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,457,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. E1397E) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248208Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134538
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457650Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725266
GnomAD4 genome Cov.: 32
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at