NM_022356.4:c.1620C>T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_022356.4(P3H1):c.1620C>T(p.Asn540Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. 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
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251126Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135770
GnomAD4 exome AF: 0.0000629 AC: 92AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.0000591 AC XY: 43AN XY: 727206
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74450
ClinVar
Submissions by phenotype
Osteogenesis Imperfecta, Recessive Uncertain:1
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Osteogenesis imperfecta type 8 Benign:1
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P3H1-related disorder Benign:1
This variant is classified as likely 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