chr10-93592104-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_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. 15/21 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
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBP4 | NM_006744.4 | c.577G>A | p.Asp193Asn | missense_variant | 6/6 | ENST00000371464.8 | |
RBP4 | NM_001323517.1 | c.577G>A | p.Asp193Asn | missense_variant | 6/6 | ||
RBP4 | NM_001323518.2 | c.571G>A | p.Asp191Asn | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBP4 | ENST00000371464.8 | c.577G>A | p.Asp193Asn | missense_variant | 6/6 | 1 | NM_006744.4 | P1 | |
RBP4 | ENST00000371467.5 | c.577G>A | p.Asp193Asn | missense_variant | 6/6 | 5 | P1 | ||
RBP4 | ENST00000371469.2 | c.571G>A | p.Asp191Asn | missense_variant | 6/6 | 5 | |||
FFAR4 | ENST00000604414.1 | c.697-11970C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251316Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461792Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 727204
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 2020 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RBP4-related conditions. This variant is present in population databases (rs777620177, ExAC 0.004%). This sequence change replaces aspartic acid with asparagine at codon 193 of the RBP4 protein (p.Asp193Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at