rs142093416
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000092.5(COL4A4):āc.2045A>Gā(p.Asp682Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000636 in 1,604,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000092.5 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 |
---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.2045A>G | p.Asp682Gly | missense_variant | 26/48 | ENST00000396625.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.2045A>G | p.Asp682Gly | missense_variant | 26/48 | 5 | NM_000092.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 151818Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000721 AC: 18AN: 249526Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135388
GnomAD4 exome AF: 0.0000668 AC: 97AN: 1452544Hom.: 0 Cov.: 29 AF XY: 0.0000747 AC XY: 54AN XY: 723318
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 151936Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74264
ClinVar
Submissions by phenotype
Autosomal recessive Alport syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 31, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL4A4 related disorder (PMID:23967202, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000072, PM2_M). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. - |
Alport syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 12, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jul 13, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | Observed in the heterozygous state in a individual with hearing loss in the published literature, however, information was limited (Miyagawa et al., 2013); Observed in a patient with thin basement nephropathy in the published literature; this variant was also noted in the same study to be observed in 143 controls in the Korean population (Baek et al., 2009); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease; This variant is associated with the following publications: (PMID: 19675380, 23967202) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at