2-99068884-A-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_025244.4(TSGA10):c.1218+4T>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,378,796 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0059 ( 32 hom. )
Consequence
TSGA10
NM_025244.4 splice_donor_region, intron
NM_025244.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0006543
2
Clinical Significance
Conservation
PhyloP100: -0.137
Genes affected
TSGA10 (HGNC:14927): (testis specific 10) Predicted to enable structural molecule activity. Predicted to be involved in spermatogenesis. Predicted to act upstream of or within cell projection assembly. Predicted to be located in neuron projection; sperm fibrous sheath; and sperm principal piece. Implicated in spermatogenic failure 26. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-99068884-A-C is Benign according to our data. Variant chr2-99068884-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 773485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 32 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSGA10 | NM_025244.4 | c.1218+4T>G | splice_donor_region_variant, intron_variant | ENST00000393483.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSGA10 | ENST00000393483.8 | c.1218+4T>G | splice_donor_region_variant, intron_variant | 1 | NM_025244.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00515 AC: 784AN: 152104Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00522 AC: 833AN: 159488Hom.: 2 AF XY: 0.00548 AC XY: 488AN XY: 88992
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GnomAD4 exome AF: 0.00594 AC: 7287AN: 1226574Hom.: 32 Cov.: 18 AF XY: 0.00586 AC XY: 3557AN XY: 606726
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GnomAD4 genome AF: 0.00516 AC: 785AN: 152222Hom.: 1 Cov.: 32 AF XY: 0.00525 AC XY: 391AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | TSGA10: BP4, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 31, 2018 | - - |
TSGA10-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 28, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at