10-93592104-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM1PP2BP4_Moderate
The NM_006744.4(RBP4):c.577G>A(p.Asp193Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006744.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBP4 | NM_006744.4 | c.577G>A | p.Asp193Asn | missense_variant | Exon 6 of 6 | ENST00000371464.8 | NP_006735.2 | |
RBP4 | NM_001323517.1 | c.577G>A | p.Asp193Asn | missense_variant | Exon 6 of 6 | NP_001310446.1 | ||
RBP4 | NM_001323518.2 | c.571G>A | p.Asp191Asn | missense_variant | Exon 6 of 6 | NP_001310447.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RBP4 | ENST00000371464.8 | c.577G>A | p.Asp193Asn | missense_variant | Exon 6 of 6 | 1 | NM_006744.4 | ENSP00000360519.3 | ||
RBP4 | ENST00000371467.5 | c.577G>A | p.Asp193Asn | missense_variant | Exon 6 of 6 | 5 | ENSP00000360522.1 | |||
RBP4 | ENST00000371469.2 | c.571G>A | p.Asp191Asn | missense_variant | Exon 6 of 6 | 5 | ENSP00000360524.2 | |||
FFAR4 | ENST00000604414.1 | c.697-11970C>T | intron_variant | Intron 2 of 2 | 3 | ENSP00000474477.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000199 AC: 5AN: 251316 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461792Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 727204 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 193 of the RBP4 protein (p.Asp193Asn). This variant is present in population databases (rs777620177, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with RBP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1057567). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at