chr2-227248443-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000091.5(COL4A3):āc.469G>Cā(p.Gly157Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000561 in 1,603,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000091.5 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A3 | NM_000091.5 | c.469G>C | p.Gly157Arg | missense_variant, splice_region_variant | 9/52 | ENST00000396578.8 | |
MFF-DT | NR_102371.1 | n.1593-10269C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A3 | ENST00000396578.8 | c.469G>C | p.Gly157Arg | missense_variant, splice_region_variant | 9/52 | 1 | NM_000091.5 | P1 | |
MFF-DT | ENST00000439598.6 | n.1593-10269C>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249350Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135312
GnomAD4 exome AF: 0.00000551 AC: 8AN: 1451622Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8AN XY: 722778
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 20, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 157 of the COL4A3 protein (p.Gly157Arg). This variant is present in population databases (rs764451365, gnomAD 0.006%). This missense change has been observed in individual(s) with bilateral sensorineural hearing loss (PMID: 23967202). ClinVar contains an entry for this variant (Variation ID: 550529). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 09, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2020 | - - |
Autosomal recessive Alport syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 27, 2017 | - - |
Benign familial hematuria;C4746745:Autosomal recessive Alport syndrome;C5882663:Autosomal dominant Alport syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 20, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at