8-39645339-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014237.3(ADAM18):āc.911A>Cā(p.Tyr304Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_014237.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAM18 | NM_014237.3 | c.911A>C | p.Tyr304Ser | missense_variant, splice_region_variant | 11/20 | ENST00000265707.10 | NP_055052.1 | |
ADAM18 | NM_001320313.2 | c.839A>C | p.Tyr280Ser | missense_variant, splice_region_variant | 10/19 | NP_001307242.1 | ||
ADAM18 | NR_135201.2 | n.788A>C | splice_region_variant, non_coding_transcript_exon_variant | 10/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAM18 | ENST00000265707.10 | c.911A>C | p.Tyr304Ser | missense_variant, splice_region_variant | 11/20 | 1 | NM_014237.3 | ENSP00000265707.5 | ||
ADAM18 | ENST00000379866.5 | c.839A>C | p.Tyr280Ser | missense_variant, splice_region_variant | 10/19 | 1 | ENSP00000369195.1 | |||
ADAM18 | ENST00000520087.5 | n.*385A>C | splice_region_variant, non_coding_transcript_exon_variant | 10/18 | 1 | ENSP00000428083.1 | ||||
ADAM18 | ENST00000520087.5 | n.*385A>C | 3_prime_UTR_variant | 10/18 | 1 | ENSP00000428083.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74284
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 25, 2024 | The c.911A>C (p.Y304S) alteration is located in exon 11 (coding exon 11) of the ADAM18 gene. This alteration results from a A to C substitution at nucleotide position 911, causing the tyrosine (Y) at amino acid position 304 to be replaced by a serine (S). 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