16-54931434-TCTC-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_005853.6(IRX5):c.240_242delCTC(p.Ser81del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000158 in 1,587,832 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005853.6 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IRX5 | NM_005853.6 | c.240_242delCTC | p.Ser81del | disruptive_inframe_deletion | Exon 1 of 3 | ENST00000394636.9 | NP_005844.4 | |
IRX5 | NM_001252197.1 | c.240_242delCTC | p.Ser81del | disruptive_inframe_deletion | Exon 1 of 3 | NP_001239126.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IRX5 | ENST00000394636.9 | c.240_242delCTC | p.Ser81del | disruptive_inframe_deletion | Exon 1 of 3 | 3 | NM_005853.6 | ENSP00000378132.4 | ||
IRX5 | ENST00000320990.9 | c.240_242delCTC | p.Ser81del | disruptive_inframe_deletion | Exon 1 of 3 | 1 | ENSP00000316250.5 | |||
IRX5 | ENST00000560154.5 | c.240_242delCTC | p.Ser81del | disruptive_inframe_deletion | Exon 1 of 3 | 5 | ENSP00000453660.1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152104Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000231 AC: 48AN: 207514Hom.: 1 AF XY: 0.000181 AC XY: 21AN XY: 116326
GnomAD4 exome AF: 0.000157 AC: 226AN: 1435614Hom.: 1 AF XY: 0.000167 AC XY: 119AN XY: 713984
GnomAD4 genome AF: 0.000164 AC: 25AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74418
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.240_242delCTC (p.S81del) alteration is located in exon 1 (coding exon 1) of the IRX5 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.240 and c.242, resulting in the deletion of 1 residue. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Craniofacial dysplasia - osteopenia syndrome Uncertain:1
Our laboratory reported dual molecular diagnoses in IRX5 (NM_005853.5:c.1362_1368delinsGT; NM_005853.5:c.240_242delCTC; in trans) and HDAC8 (NM_018486.2:c.527A>G) in an individual with delayed motor milestones, short stature, delayed speech, intellectual disability, failure to thrive, hypotonia, dysmorphic features, microcephaly, mild hearing loss, myopia, and skeletal abnormalities. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at