8-31141704-T-C
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000553.6(WRN):c.3162T>C(p.Ala1054Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A1054A) has been classified as Likely benign.
Frequency
Consequence
NM_000553.6 synonymous
Scores
Clinical Significance
Conservation
Publications
- Werner syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
- osteosarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000553.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WRN | NM_000553.6 | MANE Select | c.3162T>C | p.Ala1054Ala | synonymous | Exon 26 of 35 | NP_000544.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| WRN | ENST00000298139.7 | TSL:1 MANE Select | c.3162T>C | p.Ala1054Ala | synonymous | Exon 26 of 35 | ENSP00000298139.5 | ||
| WRN | ENST00000521620.5 | TSL:1 | n.1795T>C | non_coding_transcript_exon | Exon 14 of 23 | ||||
| WRN | ENST00000650667.1 | n.*2776T>C | non_coding_transcript_exon | Exon 25 of 34 | ENSP00000498593.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251408 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461870Hom.: 0 Cov.: 49 AF XY: 0.00000138 AC XY: 1AN XY: 727236 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380 show subpopulations
ClinVar
ClinVar submissions as Germline
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at