chr9-114156007-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_032888.4(COL27A1):c.62+1delG variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,296,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_032888.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151380Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000428 AC: 4AN: 93456Hom.: 0 AF XY: 0.0000186 AC XY: 1AN XY: 53788
GnomAD4 exome AF: 0.0000201 AC: 23AN: 1145612Hom.: 0 Cov.: 31 AF XY: 0.0000182 AC XY: 10AN XY: 549230
GnomAD4 genome AF: 0.0000264 AC: 4AN: 151380Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 73926
ClinVar
Submissions by phenotype
Steel syndrome Pathogenic:3
As part of Carrier Screening testing performed at First Genomix Laboratory, this variant was identified in a heterozygous state in several patients who were not affected with this condition. This variant is predicted by multiple in silico methods to have a deleterious effect on the protein structure and/or function. -
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (Splice site) in the COL27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL27A1 are known to be pathogenic (PMID: 24986830, 28276056). This variant is present in population databases (rs756877794, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with COL27A1-related conditions. This variant is also known as c.62+1del. ClinVar contains an entry for this variant (Variation ID: 967932). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at