rs137853153
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_000057.4(BLM):c.3107G>A(p.Cys1036Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1036F) has been classified as Pathogenic.
Frequency
Consequence
NM_000057.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.3107G>A | p.Cys1036Tyr | missense_variant | 16/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.3107G>A | p.Cys1036Tyr | missense_variant | 16/22 | 1 | NM_000057.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1454106Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 723414
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2021 | The p.C1036Y variant (also known as c.3107G>A), located in coding exon 15 of the BLM gene, results from a G to A substitution at nucleotide position 3107. The cysteine at codon 1036 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at