chrX-108591223-T-G
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_033380.3(COL4A5):āc.1331T>Gā(p.Ile444Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,206,143 control chromosomes in the GnomAD database, including 2,714 homozygotes. There are 8,304 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I444V) has been classified as Likely benign.
Frequency
Consequence
NM_033380.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.1331T>G | p.Ile444Ser | missense_variant | 20/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.1331T>G | p.Ile444Ser | missense_variant | 20/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000483338.1 | c.155T>G | p.Ile52Ser | missense_variant | 4/20 | 1 | |||
COL4A5 | ENST00000361603.7 | c.1331T>G | p.Ile444Ser | missense_variant | 20/51 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.104 AC: 11646AN: 111986Hom.: 1300 Cov.: 23 AF XY: 0.0950 AC XY: 3247AN XY: 34186
GnomAD3 exomes AF: 0.0447 AC: 8115AN: 181571Hom.: 685 AF XY: 0.0334 AC XY: 2228AN XY: 66621
GnomAD4 exome AF: 0.0160 AC: 17507AN: 1094106Hom.: 1414 Cov.: 30 AF XY: 0.0140 AC XY: 5042AN XY: 360496
GnomAD4 genome AF: 0.104 AC: 11658AN: 112037Hom.: 1300 Cov.: 23 AF XY: 0.0952 AC XY: 3262AN XY: 34247
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 07, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 22, 2017 | p.Ile444Ser in exon 20 of COL4A5: This variant is not expected to have clinical significance because it has been identified in 34% (6123/17969) of African chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org; dbSNP rs2272946). ACMG/AMP Criteria applied: BA1. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
X-linked Alport syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 03, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 21, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 8648925, 27884173, 11223851, 10561141, 8940267, 30245029) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 16, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at