chr11-66721149-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 3P and 13B. PM1PP2BP4_StrongBP6BS1BS2
The NM_006946.4(SPTBN2):c.92C>T(p.Ser31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,614,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S31P) has been classified as Uncertain significance.
Frequency
Consequence
NM_006946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTBN2 | NM_006946.4 | c.92C>T | p.Ser31Leu | missense_variant | 3/38 | ENST00000533211.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTBN2 | ENST00000533211.6 | c.92C>T | p.Ser31Leu | missense_variant | 3/38 | 5 | NM_006946.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000546 AC: 83AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000521 AC: 131AN: 251472Hom.: 0 AF XY: 0.000574 AC XY: 78AN XY: 135908
GnomAD4 exome AF: 0.000951 AC: 1390AN: 1461894Hom.: 4 Cov.: 31 AF XY: 0.000898 AC XY: 653AN XY: 727248
GnomAD4 genome AF: 0.000545 AC: 83AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74420
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 31, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2022 | Unlikely to be causative of SPTBN2-related spinocerebellar ataxia (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spinocerebellar ataxia type 5;C4706415:Autosomal recessive spinocerebellar ataxia 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Aug 27, 2021 | ACMG classification criteria: BP4 supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at