19-6718376-G-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_000064.4(C3):āc.304C>Gā(p.Arg102Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,614,024 control chromosomes in the GnomAD database, including 31,345 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000064.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C3 | NM_000064.4 | c.304C>G | p.Arg102Gly | missense_variant | 3/41 | ENST00000245907.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C3 | ENST00000245907.11 | c.304C>G | p.Arg102Gly | missense_variant | 3/41 | 1 | NM_000064.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.141 AC: 21517AN: 152112Hom.: 2011 Cov.: 32
GnomAD3 exomes AF: 0.150 AC: 37843AN: 251466Hom.: 3504 AF XY: 0.155 AC XY: 21120AN XY: 135908
GnomAD4 exome AF: 0.192 AC: 281032AN: 1461794Hom.: 29334 Cov.: 38 AF XY: 0.191 AC XY: 138972AN XY: 727206
GnomAD4 genome ? AF: 0.141 AC: 21521AN: 152230Hom.: 2011 Cov.: 32 AF XY: 0.139 AC XY: 10331AN XY: 74414
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | This variant is associated with the following publications: (PMID: 29485352, 30131807, 25322978, 7870343, 20385819, 21555552, 24736606, 19823576, 19168221, 17634448, 24036950, 24036949, 20664795, 25488663, 21784901, 18325906, 25688879, 25087612) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Age related macular degeneration 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
C3S/C3F POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Apr 01, 2013 | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 27, 2022 | - - |
MACULAR DEGENERATION, AGE-RELATED, 9, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Apr 01, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at