16-89959153-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001242818.2(DEF8):āc.512C>Gā(p.Thr171Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000016 ( 0 hom. )
Consequence
DEF8
NM_001242818.2 missense, splice_region
NM_001242818.2 missense, splice_region
Scores
4
7
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.30
Genes affected
DEF8 (HGNC:25969): (differentially expressed in FDCP 8 homolog) Predicted to enable metal ion binding activity. Predicted to be involved in lysosome localization; positive regulation of bone resorption; and positive regulation of ruffle assembly. [provided by Alliance of Genome Resources, Apr 2022]
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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 | UniProt |
---|---|---|---|---|---|---|---|
DEF8 | NM_001242818.2 | c.512C>G | p.Thr171Arg | missense_variant, splice_region_variant | 6/13 | ENST00000563594.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEF8 | ENST00000563594.6 | c.512C>G | p.Thr171Arg | missense_variant, splice_region_variant | 6/13 | 1 | NM_001242818.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251086Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135800
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461598Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727070
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.;N;N;N;N;N;N;N;N
Sift
Uncertain
D;.;.;D;T;D;D;D;T;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Polyphen
B;D;B;.;B;.;B;D;.;B;.
Vest4
MutPred
0.55
.;.;.;.;Gain of MoRF binding (P = 0.0838);.;.;.;.;.;.;
MVP
MPC
1.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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