rs972796332
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The NM_000091.5(COL4A3):c.3577G>A(p.Asp1193Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,608,128 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000091.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A3 | NM_000091.5 | c.3577G>A | p.Asp1193Asn | missense_variant | 42/52 | ENST00000396578.8 | |
MFF-DT | NR_102371.1 | n.243+7775C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A3 | ENST00000396578.8 | c.3577G>A | p.Asp1193Asn | missense_variant | 42/52 | 1 | NM_000091.5 | P1 | |
MFF-DT | ENST00000439598.6 | n.243+7775C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000849 AC: 2AN: 235648Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 127978
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1455948Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 723416
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 21, 2017 | p.Asp1193Asn in exon 42 of COL4A3: This variant is not expected to have clinical significance because the aspartic acid (Asp) at position 1193 is not conserved in mammals or evolutionarily distant species and 4 mammals (shrew, wallaby, opos sum, and Tasmanian devil) carry an asparagine (Asn) at this position despite nea rby amino acid sequence conservation. Additional computational prediction tools and conservation analysis suggest that the variant may not impact the protein. This variant been identified in 5/120268 of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; ). ACMG/AMP Crit eria Applied BP4_strong. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at