chr1-231241226-A-C
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_014236.4(GNPAT):c.-153A>C variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000292 in 1,504,834 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 5 hom. )
Consequence
GNPAT
NM_014236.4 5_prime_UTR
NM_014236.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.00
Genes affected
GNPAT (HGNC:4416): (glyceronephosphate O-acyltransferase) This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000118 (18/152334) while in subpopulation EAS AF= 0.00348 (18/5178). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPAT | NM_014236.4 | c.-153A>C | 5_prime_UTR_variant | 1/16 | ENST00000366647.9 | ||
GNPAT | NM_001316350.2 | c.-153A>C | 5_prime_UTR_variant | 1/15 | |||
GNPAT | XM_005273313.5 | c.-153A>C | 5_prime_UTR_variant | 1/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPAT | ENST00000366647.9 | c.-153A>C | 5_prime_UTR_variant | 1/16 | 1 | NM_014236.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152216Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000312 AC: 422AN: 1352500Hom.: 5 Cov.: 22 AF XY: 0.000332 AC XY: 225AN XY: 677212
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74494
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhizomelic chondrodysplasia punctata type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at