rs17074773
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001017995.3(SH3PXD2B):c.105C>T(p.Ser35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,610,500 control chromosomes in the GnomAD database, including 82,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 7494 hom., cov: 32)
Exomes 𝑓: 0.31 ( 74940 hom. )
Consequence
SH3PXD2B
NM_001017995.3 synonymous
NM_001017995.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.18
Genes affected
SH3PXD2B (HGNC:29242): (SH3 and PX domains 2B) This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-172422467-G-A is Benign according to our data. Variant chr5-172422467-G-A is described in ClinVar as [Benign]. Clinvar id is 257056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-172422467-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.18 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH3PXD2B | NM_001017995.3 | c.105C>T | p.Ser35= | synonymous_variant | 2/13 | ENST00000311601.6 | |
SH3PXD2B | NM_001308175.2 | c.105C>T | p.Ser35= | synonymous_variant | 2/13 | ||
SH3PXD2B | XM_017009351.2 | c.105C>T | p.Ser35= | synonymous_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH3PXD2B | ENST00000311601.6 | c.105C>T | p.Ser35= | synonymous_variant | 2/13 | 1 | NM_001017995.3 | P1 | |
SH3PXD2B | ENST00000519643.5 | c.105C>T | p.Ser35= | synonymous_variant | 2/13 | 1 | |||
SH3PXD2B | ENST00000636523.1 | c.63C>T | p.Ser21= | synonymous_variant | 2/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.301 AC: 45702AN: 151786Hom.: 7481 Cov.: 32
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GnomAD3 exomes AF: 0.351 AC: 86604AN: 246870Hom.: 17100 AF XY: 0.345 AC XY: 46107AN XY: 133482
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GnomAD4 exome AF: 0.312 AC: 454464AN: 1458596Hom.: 74940 Cov.: 40 AF XY: 0.313 AC XY: 226690AN XY: 725382
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GnomAD4 genome ? AF: 0.301 AC: 45745AN: 151904Hom.: 7494 Cov.: 32 AF XY: 0.307 AC XY: 22757AN XY: 74230
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2018 | - - |
Frank-Ter Haar syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at