rs116214830
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM2BP4_StrongBP6BS1
The NM_000232.5(SGCB):c.794C>T(p.Thr265Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T265T) has been classified as Likely benign.
Frequency
Consequence
NM_000232.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCB | NM_000232.5 | c.794C>T | p.Thr265Ile | missense_variant | 6/6 | ENST00000381431.10 | |
SGCB | XM_047416074.1 | c.584C>T | p.Thr195Ile | missense_variant | 5/5 | ||
SGCB | XM_047416075.1 | c.497C>T | p.Thr166Ile | missense_variant | 5/5 | ||
SGCB | XM_047416076.1 | c.497C>T | p.Thr166Ile | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCB | ENST00000381431.10 | c.794C>T | p.Thr265Ile | missense_variant | 6/6 | 1 | NM_000232.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251454Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135894
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727218
GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74480
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2E Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 265 of the SGCB protein (p.Thr265Ile). This variant is present in population databases (rs116214830, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SGCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 282121). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SGCB 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 04, 2021 | The SGCB c.794C>T, p.Thr265Ile variant (rs116214830), to our knowledge, is not reported in the medical literature but is reported as uncertain in ClinVar (Variation ID: 282121). This variant is found in the African population with an allele frequency of 0.1% (28/24,964 alleles) in the Genome Aggregation Database. The threonine at codon 265 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.31). Due to limited information, the clinical significance of the p.Thr265Ile variant is uncertain at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 02, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 23, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2019 | - - |
Primary dilated cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | research | Genetics and Genomics Program, Sidra Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at