rs587702260
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_013314.4(BLNK):āc.254T>Cā(p.Val85Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V85M) has been classified as Uncertain significance.
Frequency
Consequence
NM_013314.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLNK | NM_013314.4 | c.254T>C | p.Val85Ala | missense_variant | 5/17 | ENST00000224337.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLNK | ENST00000224337.10 | c.254T>C | p.Val85Ala | missense_variant | 5/17 | 1 | NM_013314.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251436Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135902
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461840Hom.: 0 Cov.: 37 AF XY: 0.0000151 AC XY: 11AN XY: 727228
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74518
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2022 | The c.254T>C (p.V85A) alteration is located in exon 5 (coding exon 5) of the BLNK gene. This alteration results from a T to C substitution at nucleotide position 254, causing the valine (V) at amino acid position 85 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Agammaglobulinemia 4, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2022 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 85 of the BLNK protein (p.Val85Ala). This variant is present in population databases (rs587702260, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BLNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 575592). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at