chr10-126043148-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001288973.2(ADAM12):c.1996G>C(p.Val666Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001288973.2 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM12 | NM_001288973.2 | c.1996G>C | p.Val666Leu | missense_variant, splice_region_variant | 18/23 | ENST00000448723.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM12 | ENST00000448723.2 | c.1996G>C | p.Val666Leu | missense_variant, splice_region_variant | 18/23 | 5 | NM_001288973.2 | A2 | |
ADAM12 | ENST00000368679.8 | c.2005G>C | p.Val669Leu | missense_variant, splice_region_variant | 18/23 | 1 | P2 | ||
ADAM12 | ENST00000368676.8 | c.2005G>C | p.Val669Leu | missense_variant, splice_region_variant | 18/19 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250750Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135530
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727152
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2023 | The c.2005G>C (p.V669L) alteration is located in exon 18 (coding exon 18) of the ADAM12 gene. This alteration results from a G to C substitution at nucleotide position 2005, causing the valine (V) at amino acid position 669 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at