rs397516560
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001368067.1(LDB3):āc.775C>Gā(p.Arg259Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,520 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001368067.1 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 |
---|---|---|---|---|---|---|---|
LDB3 | NM_001368067.1 | c.775C>G | p.Arg259Gly | missense_variant | 9/9 | ENST00000263066.11 | |
LDB3 | NM_007078.3 | c.896+6726C>G | intron_variant | ENST00000361373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LDB3 | ENST00000263066.11 | c.775C>G | p.Arg259Gly | missense_variant | 9/9 | 1 | NM_001368067.1 | ||
LDB3 | ENST00000361373.9 | c.896+6726C>G | intron_variant | 1 | NM_007078.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461520Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727046
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 12, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Arg259Gly varia nt in LDB3 has not been previously reported in the literature and was not identi fied in large and broad populations by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS). This variant has been observed in one individual o f Ashkenazi Jewish ancestry with LVNC tested by our laboratory. Computational an alyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, a nd SIFT) suggest that the Arg259Gly variant may not impact the normal function o f the protein, though these tools are not predictive enough to rule out pathogen icity. The observed low frequency of this variant in the general population is c onsistent with a disease-causing role but insufficient to establish this with co nfidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at