8-39637539-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014237.3(ADAM18):c.663G>A(p.Met221Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,606,246 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014237.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAM18 | NM_014237.3 | c.663G>A | p.Met221Ile | missense_variant, splice_region_variant | 9/20 | ENST00000265707.10 | NP_055052.1 | |
ADAM18 | NM_001320313.2 | c.591G>A | p.Met197Ile | missense_variant, splice_region_variant | 8/19 | NP_001307242.1 | ||
ADAM18 | NR_135201.2 | n.540G>A | splice_region_variant, non_coding_transcript_exon_variant | 8/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAM18 | ENST00000265707.10 | c.663G>A | p.Met221Ile | missense_variant, splice_region_variant | 9/20 | 1 | NM_014237.3 | ENSP00000265707 | P1 | |
ADAM18 | ENST00000379866.5 | c.591G>A | p.Met197Ile | missense_variant, splice_region_variant | 8/19 | 1 | ENSP00000369195 | |||
ADAM18 | ENST00000520087.5 | c.*137G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 8/18 | 1 | ENSP00000428083 |
Frequencies
GnomAD3 genomes AF: 0.000270 AC: 41AN: 151918Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000427 AC: 105AN: 245890Hom.: 1 AF XY: 0.000354 AC XY: 47AN XY: 132932
GnomAD4 exome AF: 0.000248 AC: 361AN: 1454328Hom.: 2 Cov.: 30 AF XY: 0.000252 AC XY: 182AN XY: 723296
GnomAD4 genome AF: 0.000270 AC: 41AN: 151918Hom.: 0 Cov.: 31 AF XY: 0.000283 AC XY: 21AN XY: 74188
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.663G>A (p.M221I) alteration is located in exon 9 (coding exon 9) of the ADAM18 gene. This alteration results from a G to A substitution at nucleotide position 663, causing the methionine (M) at amino acid position 221 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | ADAM18: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at