NM_021023.6:c.99_105delATTTCAT
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_021023.6(CFHR3):c.99_105delATTTCAT(p.Phe34ArgfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000974 in 1,530,002 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000044 ( 1 hom., cov: 25)
Exomes 𝑓: 0.00010 ( 28 hom. )
Consequence
CFHR3
NM_021023.6 frameshift
NM_021023.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.90
Genes affected
CFHR3 (HGNC:16980): (complement factor H related 3) The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 28 AD,AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFHR3 | NM_021023.6 | c.99_105delATTTCAT | p.Phe34ArgfsTer10 | frameshift_variant | Exon 2 of 6 | ENST00000367425.9 | NP_066303.2 | |
CFHR3 | NM_001166624.2 | c.99_105delATTTCAT | p.Phe34ArgfsTer10 | frameshift_variant | Exon 2 of 5 | NP_001160096.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFHR3 | ENST00000367425.9 | c.99_105delATTTCAT | p.Phe34ArgfsTer10 | frameshift_variant | Exon 2 of 6 | 1 | NM_021023.6 | ENSP00000356395.5 | ||
ENSG00000289697 | ENST00000696032.1 | c.3621_3627delATTTCAT | p.Phe1208ArgfsTer10 | frameshift_variant | Exon 23 of 27 | ENSP00000512341.1 |
Frequencies
GnomAD3 genomes AF: 0.0000438 AC: 6AN: 136962Hom.: 1 Cov.: 25
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GnomAD3 exomes AF: 0.0000252 AC: 6AN: 238034Hom.: 1 AF XY: 0.0000312 AC XY: 4AN XY: 128362
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GnomAD4 exome AF: 0.000103 AC: 143AN: 1393040Hom.: 28 AF XY: 0.0000925 AC XY: 64AN XY: 691796
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GnomAD4 genome AF: 0.0000438 AC: 6AN: 136962Hom.: 1 Cov.: 25 AF XY: 0.0000451 AC XY: 3AN XY: 66564
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Age related macular degeneration 1;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1 Uncertain:1
Sep 26, 2022
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research
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Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at