rs78972735
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_033380.3(COL4A5):c.2858G>T(p.Gly953Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,209,432 control chromosomes in the GnomAD database, including 8 homozygotes. There are 474 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G953G) 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 -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.2858G>T | p.Gly953Val | missense_variant | 33/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.2858G>T | p.Gly953Val | missense_variant | 33/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000483338.1 | c.1682G>T | p.Gly561Val | missense_variant | 17/20 | 1 | |||
COL4A5 | ENST00000361603.7 | c.2858G>T | p.Gly953Val | missense_variant | 33/51 | 2 | P1 | ||
COL4A5 | ENST00000505728.1 | c.92G>T | p.Gly31Val | missense_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00159 AC: 179AN: 112429Hom.: 0 Cov.: 23 AF XY: 0.00208 AC XY: 72AN XY: 34609
GnomAD3 exomes AF: 0.00360 AC: 659AN: 182930Hom.: 7 AF XY: 0.00337 AC XY: 228AN XY: 67596
GnomAD4 exome AF: 0.00104 AC: 1146AN: 1096952Hom.: 8 Cov.: 30 AF XY: 0.00111 AC XY: 403AN XY: 362498
GnomAD4 genome ? AF: 0.00158 AC: 178AN: 112480Hom.: 0 Cov.: 23 AF XY: 0.00205 AC XY: 71AN XY: 34670
ClinVar
Submissions by phenotype
X-linked Alport syndrome Uncertain:1Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | Aug 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 16, 2020 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 21, 2017 | p.Gly953Val in exon 33 of COL4A5: This variant is not expected to have clinica l significance, because it has been identified in 3.7% (513/13865) of East Asian chromosomes including 7 homozygotes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs104886203, rs78972735). Although it has been reported in several individuals with Alport syndrome or hearing loss, 2 individuals with Alport syndrome had another COL4A5 variant in cis with this va riant, and one individual was reported to have polycystic kidney disease with no additional clinical features of Alport syndrome (Knebelmann 1996, Lennon 2015, Miao 2017, Miyagawa 2013, Nishio 2015, Randles 2016, Tan 2010). In summary, it s frequency is too high to be causative for Alport syndrome. ACMG/AMP criteria a pplied: BA1 - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 13, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2019 | This variant is associated with the following publications: (PMID: 22995991, 28827396, 30577881, 30367527, 25739341, 23967202, 8940267, 30245029, 31138263, 28476686, 31180159, 32038292) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Kidney disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 24, 2021 | - - |
COL4A5-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 20, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at