19-40472704-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020971.3(SPTBN4):c.83C>T(p.Pro28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,836 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 Uncertain significance (★★).
Frequency
Consequence
NM_020971.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPTBN4 | ENST00000598249.6 | c.83C>T | p.Pro28Leu | missense_variant | Exon 2 of 36 | 1 | NM_020971.3 | ENSP00000469242.1 | ||
SPTBN4 | ENST00000352632.7 | c.83C>T | p.Pro28Leu | missense_variant | Exon 2 of 36 | 5 | ENSP00000263373.2 | |||
SPTBN4 | ENST00000595535.5 | c.83C>T | p.Pro28Leu | missense_variant | Exon 2 of 27 | 5 | ENSP00000470693.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246664Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 133960
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460688Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726526
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.83C>T (p.P28L) alteration is located in exon 2 (coding exon 1) of the SPTBN4 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the proline (P) at amino acid position 28 to be replaced by a leucine (L). Based on data from gnomAD, the T allele has an overall frequency of <0.01% (1/246664) total alleles studied. This amino acid position is conserved in available mammalian species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at