rs201117318
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001039141.3(TRIOBP):c.4783C>T(p.Arg1595Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000082 in 1,609,002 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1595H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001039141.3 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 |
---|---|---|---|---|---|---|---|
TRIOBP | NM_001039141.3 | c.4783C>T | p.Arg1595Cys | missense_variant | 9/24 | ENST00000644935.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRIOBP | ENST00000644935.1 | c.4783C>T | p.Arg1595Cys | missense_variant | 9/24 | NM_001039141.3 | A2 | ||
TRIOBP | ENST00000344404.10 | c.*4266C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000322 AC: 49AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000134 AC: 33AN: 245650Hom.: 1 AF XY: 0.0000969 AC XY: 13AN XY: 134126
GnomAD4 exome AF: 0.0000570 AC: 83AN: 1456750Hom.: 1 Cov.: 36 AF XY: 0.0000497 AC XY: 36AN XY: 723748
GnomAD4 genome ? AF: 0.000322 AC: 49AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 12, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 15, 2021 | The c.4783C>T (p.R1595C) alteration is located in exon 9 (coding exon 7) of the TRIOBP gene. This alteration results from a C to T substitution at nucleotide position 4783, causing the arginine (R) at amino acid position 1595 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 17, 2015 | Arg1595Cys in exon 9 of TRIOBP: This variant is not expected to have clinical si gnificance because the arginine (Arg) residue at position 1595 is not conserved through species, with 8 mammals having a cystine (Cys) at this position. It has been identified in 0.15% (14/9258) of African chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201117318). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at