1-42750280-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_022356.4(P3H1):c.1626G>A(p.Thr542Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,054 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_022356.4 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000789 AC: 120AN: 152156Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00268 AC: 672AN: 251008Hom.: 13 AF XY: 0.00341 AC XY: 463AN XY: 135686
GnomAD4 exome AF: 0.00128 AC: 1876AN: 1461780Hom.: 29 Cov.: 32 AF XY: 0.00180 AC XY: 1307AN XY: 727174
GnomAD4 genome AF: 0.000788 AC: 120AN: 152274Hom.: 2 Cov.: 32 AF XY: 0.00111 AC XY: 83AN XY: 74458
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:3
- -
- -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Osteogenesis Imperfecta, Recessive Uncertain:1
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. -
Osteogenesis imperfecta Benign:1
- -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at