rs128621191
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000061.3(BTK):c.718G>T(p.Glu240Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
BTK
NM_000061.3 stop_gained
NM_000061.3 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 5.54
Genes affected
BTK (HGNC:1133): (Bruton tyrosine kinase) The protein encoded by this gene plays a crucial role in B-cell development. Mutations in this gene cause X-linked agammaglobulinemia type 1, which is an immunodeficiency characterized by the failure to produce mature B lymphocytes, and associated with a failure of Ig heavy chain rearrangement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-101360626-C-A is Pathogenic according to our data. Variant chrX-101360626-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11361.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-101360626-C-A is described in Lovd as [Pathogenic]. Variant chrX-101360626-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTK | NM_000061.3 | c.718G>T | p.Glu240Ter | stop_gained | 8/19 | ENST00000308731.8 | |
BTK | NM_001287344.2 | c.820G>T | p.Glu274Ter | stop_gained | 8/19 | ||
BTK | NM_001287345.2 | c.718G>T | p.Glu240Ter | stop_gained | 9/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTK | ENST00000308731.8 | c.718G>T | p.Glu240Ter | stop_gained | 8/19 | 1 | NM_000061.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
X-linked agammaglobulinemia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1994 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at