rs786205170
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000124.4(ERCC6):c.3412_3413insA(p.Thr1138AsnfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T1138T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000124.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERCC6 | NM_000124.4 | c.3412_3413insA | p.Thr1138AsnfsTer7 | frameshift_variant | 18/21 | ENST00000355832.10 | |
ERCC6 | NM_001346440.2 | c.3412_3413insA | p.Thr1138AsnfsTer7 | frameshift_variant | 18/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERCC6 | ENST00000355832.10 | c.3412_3413insA | p.Thr1138AsnfsTer7 | frameshift_variant | 18/21 | 1 | NM_000124.4 | P1 | |
ENST00000423283.1 | n.235-2152dup | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461862Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727226
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cerebrooculofacioskeletal syndrome 1;C0265201:DE SANCTIS-CACCHIONE SYNDROME;C0751038:Cockayne syndrome type 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jul 31, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 190166). This variant has not been reported in the literature in individuals affected with ERCC6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1138Asnfs*7) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). - |
Cockayne syndrome type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Claritas Genomics | Nov 18, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at