rs28936397
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_000557.5(GDF5):c.517A>G(p.Met173Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M173I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000557.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF5 | NM_000557.5 | c.517A>G | p.Met173Val | missense_variant | 1/2 | ENST00000374369.8 | |
GDF5 | NM_001319138.2 | c.517A>G | p.Met173Val | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF5 | ENST00000374369.8 | c.517A>G | p.Met173Val | missense_variant | 1/2 | 1 | NM_000557.5 | P1 | |
GDF5 | ENST00000374372.1 | c.517A>G | p.Met173Val | missense_variant | 3/4 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251252Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135802
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461392Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726998
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Brachydactyly type C Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2004 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at