1-42757818-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_022356.4(P3H1):c.1045G>A(p.Gly349Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,614,128 control chromosomes in the GnomAD database, including 1,950 homozygotes. 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. G349G) has been classified as Likely benign.
Frequency
Consequence
NM_022356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0586 AC: 8914AN: 152172Hom.: 359 Cov.: 32
GnomAD3 exomes AF: 0.0438 AC: 11010AN: 251490Hom.: 304 AF XY: 0.0442 AC XY: 6003AN XY: 135916
GnomAD4 exome AF: 0.0430 AC: 62829AN: 1461838Hom.: 1589 Cov.: 32 AF XY: 0.0433 AC XY: 31456AN XY: 727228
GnomAD4 genome AF: 0.0586 AC: 8930AN: 152290Hom.: 361 Cov.: 32 AF XY: 0.0577 AC XY: 4299AN XY: 74478
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 06, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 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. - |
Osteogenesis Imperfecta, Recessive Uncertain:1
Uncertain significance, 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 06, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at