chr8-24311367-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014265.6(ADAM28):c.313T>A(p.Cys105Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,612,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ADAM28
NM_014265.6 missense
NM_014265.6 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 3.59
Genes affected
ADAM28 (HGNC:206): (ADAM metallopeptidase domain 28) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins 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. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. This gene is present in a gene cluster with other members of the ADAM family on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAM28 | NM_014265.6 | c.313T>A | p.Cys105Ser | missense_variant | 5/23 | ENST00000265769.9 | NP_055080.2 | |
ADAM7-AS1 | NR_125808.1 | n.502-10438A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAM28 | ENST00000265769.9 | c.313T>A | p.Cys105Ser | missense_variant | 5/23 | 1 | NM_014265.6 | ENSP00000265769 | A2 | |
ADAM7-AS1 | ENST00000519689.1 | n.607-10438A>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000520 AC: 13AN: 250068Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135140
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460164Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726368
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GnomAD4 genome AF: 0.000322 AC: 49AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74466
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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 | Jun 27, 2023 | The c.313T>A (p.C105S) alteration is located in exon 5 (coding exon 5) of the ADAM28 gene. This alteration results from a T to A substitution at nucleotide position 313, causing the cysteine (C) at amino acid position 105 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0052);Gain of disorder (P = 0.0052);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at