11-66690113-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_006946.4(SPTBN2):c.5736C>G(p.Phe1912Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_006946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTBN2 | NM_006946.4 | c.5736C>G | p.Phe1912Leu | missense_variant | 28/38 | ENST00000533211.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTBN2 | ENST00000533211.6 | c.5736C>G | p.Phe1912Leu | missense_variant | 28/38 | 5 | NM_006946.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152268Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251162Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135788
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461890Hom.: 1 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727246
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152386Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74528
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPTBN2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 448516). This variant has not been reported in the literature in individuals affected with SPTBN2-related conditions. This variant is present in population databases (rs202247290, gnomAD 0.03%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1912 of the SPTBN2 protein (p.Phe1912Leu). - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 03, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at