rs587780249
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_032043.3(BRIP1):c.3412G>T(p.Asp1138Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,612,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1138G) has been classified as Uncertain significance.
Frequency
Consequence
NM_032043.3 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 |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.3412G>T | p.Asp1138Tyr | missense_variant | 20/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.3412G>T | p.Asp1138Tyr | missense_variant | 20/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249976Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135356
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460312Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726540
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2018 | This variant is denoted BRIP1 c.3412G>T at the cDNA level, p.Asp1138Tyr (D1138Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). This variant was observed in an individual with head and neck squamous cell carcinoma (Lu 2015). BRIP1 Asp1138Tyr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Asp1138Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 05, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The p.D1138Y variant (also known as c.3412G>T), located in coding exon 19 of the BRIP1 gene, results from a G to T substitution at nucleotide position 3412. The aspartic acid at codon 1138 is replaced by tyrosine, an amino acid with highly 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