rs759982203
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000057.4(BLM):āc.4093A>Gā(p.Arg1365Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,016 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. R1365K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000057.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLM | NM_000057.4 | c.4093A>G | p.Arg1365Gly | missense_variant | 22/22 | ENST00000355112.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLM | ENST00000355112.8 | c.4093A>G | p.Arg1365Gly | missense_variant | 22/22 | 1 | NM_000057.4 | P2 | |
ENST00000656405.1 | n.427T>C | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251438Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727224
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Bloom syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 23, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1365 of the BLM protein (p.Arg1365Gly). This variant is present in population databases (rs759982203, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 485355). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2021 | The p.R1365G variant (also known as c.4093A>G), located in coding exon 21 of the BLM gene, results from an A to G substitution at nucleotide position 4093. The arginine at codon 1365 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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