chr21-44528597-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_144991.3(TSPEAR):c.791-14G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000607 in 1,612,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144991.3 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSPEAR | NM_144991.3 | c.791-14G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000323084.9 | |||
LOC124905038 | XR_007067905.1 | n.1089C>G | non_coding_transcript_exon_variant | 1/2 | |||
TSPEAR | NM_001272037.2 | c.587-14G>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSPEAR | ENST00000323084.9 | c.791-14G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_144991.3 | P1 | |||
TSPEAR | ENST00000397916.1 | n.746-14G>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 1 | |||||
TSPEAR | ENST00000642437.1 | c.*736-14G>C | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000401 AC: 61AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000389 AC: 97AN: 249536Hom.: 0 AF XY: 0.000422 AC XY: 57AN XY: 135032
GnomAD4 exome AF: 0.000629 AC: 918AN: 1460310Hom.: 0 Cov.: 31 AF XY: 0.000625 AC XY: 454AN XY: 726472
GnomAD4 genome AF: 0.000401 AC: 61AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32AN XY: 74472
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 11, 2017 | The c.791-14G>C variant in TSPEAR has been previously reported by our laboratory in 1 individual with hearing loss, but a variant affecting the other copy of th e gene was not identified. This variant has been identified in 83/126028 Europea n chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs199699551); however, this frequency is not high enough to ru le out a pathogenic role. This variant is located in the 3' splice region. Compu tational tools do not suggest an impact to splicing. However, this information i s not predictive enough to rule out pathogenicity. In summary, the clinical sig nificance of the c.791-14G>C variant is uncertain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at