10-103602013-T-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001394015.1(SH3PXD2A):c.3205A>C(p.Ile1069Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000675 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
SH3PXD2A
NM_001394015.1 missense
NM_001394015.1 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 6.27
Genes affected
SH3PXD2A (HGNC:23664): (SH3 and PX domains 2A) Predicted to enable superoxide-generating NADPH oxidase activator activity. Involved in osteoclast fusion and superoxide metabolic process. Located in podosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3PXD2A | NM_001394015.1 | c.3205A>C | p.Ile1069Leu | missense_variant | 15/15 | ENST00000369774.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3PXD2A | ENST00000369774.9 | c.3205A>C | p.Ile1069Leu | missense_variant | 15/15 | 5 | NM_001394015.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250798Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135488
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GnomAD4 exome AF: 0.0000712 AC: 104AN: 1461484Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 46AN XY: 727014
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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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 | Dec 19, 2023 | The c.3121A>C (p.I1041L) alteration is located in exon 14 (coding exon 14) of the SH3PXD2A gene. This alteration results from a A to C substitution at nucleotide position 3121, causing the isoleucine (I) at amino acid position 1041 to be replaced by a leucine (L). 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;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at