chr10-126039347-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001288973.2(ADAM12):c.2187G>T(p.Lys729Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,614,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 1 hom. )
Consequence
ADAM12
NM_001288973.2 missense
NM_001288973.2 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 1.87
Genes affected
ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.24691659).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM12 | NM_001288973.2 | c.2187G>T | p.Lys729Asn | missense_variant | 19/23 | ENST00000448723.2 | |
ADAM12 | NM_003474.6 | c.2196G>T | p.Lys732Asn | missense_variant | 19/23 | ||
ADAM12 | XM_017016706.2 | c.1029G>T | p.Lys343Asn | missense_variant | 9/13 | ||
ADAM12 | XM_024448210.1 | c.858G>T | p.Lys286Asn | missense_variant | 8/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM12 | ENST00000448723.2 | c.2187G>T | p.Lys729Asn | missense_variant | 19/23 | 5 | NM_001288973.2 | A2 | |
ADAM12 | ENST00000368679.8 | c.2196G>T | p.Lys732Asn | missense_variant | 19/23 | 1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152124Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251492Hom.: 1 AF XY: 0.000125 AC XY: 17AN XY: 135918
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461856Hom.: 1 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727232
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74430
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2023 | The c.2196G>T (p.K732N) alteration is located in exon 19 (coding exon 19) of the ADAM12 gene. This alteration results from a G to T substitution at nucleotide position 2196, causing the lysine (K) at amino acid position 732 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at