rs149635611
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_012452.3(TNFRSF13B):c.740C>T(p.Thr247Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,609,658 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 Uncertain significance (★★).
Frequency
Consequence
NM_012452.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFRSF13B | NM_012452.3 | c.740C>T | p.Thr247Met | missense_variant | 5/5 | ENST00000261652.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFRSF13B | ENST00000261652.7 | c.740C>T | p.Thr247Met | missense_variant | 5/5 | 1 | NM_012452.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000525 AC: 13AN: 247546Hom.: 0 AF XY: 0.0000448 AC XY: 6AN XY: 134006
GnomAD4 exome AF: 0.0000762 AC: 111AN: 1457300Hom.: 0 Cov.: 35 AF XY: 0.0000898 AC XY: 65AN XY: 724174
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74504
ClinVar
Submissions by phenotype
Immunodeficiency, common variable, 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 247 of the TNFRSF13B protein (p.Thr247Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with primary antibody deficiency (PMID: 29921932). ClinVar contains an entry for this variant (Variation ID: 568673). 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 TNFRSF13B protein function with a negative predictive value of 80%. 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 | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Sep 06, 2020 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Sep 14, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Identified on exome sequencing in an individual with primary antibody deficiency who also harbored a second TNFRSF13B variant (Abolhassani et al., 2019); This variant is associated with the following publications: (PMID: 29921932) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at