chr1-231241332-C-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_014236.4(GNPAT):c.-47C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,521,028 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
GNPAT
NM_014236.4 5_prime_UTR
NM_014236.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.375
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000184 (28/152352) while in subpopulation SAS AF= 0.00145 (7/4830). AF 95% confidence interval is 0.000679. There are 0 homozygotes in gnomad4. There are 17 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
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| GNPAT | NM_014236.4 | c.-47C>A | 5_prime_UTR_variant | 1/16 | ENST00000366647.9 | ||
| GNPAT | NM_001316350.2 | c.-47C>A | 5_prime_UTR_variant | 1/15 | |||
| GNPAT | XM_005273313.5 | c.-47C>A | 5_prime_UTR_variant | 1/16 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GNPAT | ENST00000366647.9 | c.-47C>A | 5_prime_UTR_variant | 1/16 | 1 | NM_014236.4 | P1 | ||
| GNPAT | ENST00000416000.1 | c.-47C>A | 5_prime_UTR_variant | 1/13 | 5 | ||||
| GNPAT | ENST00000436239.5 | c.-47C>A | 5_prime_UTR_variant | 1/6 | 3 | ||||
| GNPAT | ENST00000644483.1 | c.-47C>A | 5_prime_UTR_variant, NMD_transcript_variant | 1/17 |
Frequencies
GnomAD3 genomes 0.000184 AC: 28AN: 152234Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
28
AN:
152234
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000280 AC: 70AN: 249778Hom.: 0 AF XY: 0.000355 AC XY: 48AN XY: 135132
GnomAD3 exomes
AF:
AC:
70
AN:
249778
Hom.:
AF XY:
AC XY:
48
AN XY:
135132
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000143 AC: 196AN: 1368676Hom.: 0 Cov.: 21 AF XY: 0.000182 AC XY: 125AN XY: 686580
GnomAD4 exome
AF:
AC:
196
AN:
1368676
Hom.:
Cov.:
21
AF XY:
AC XY:
125
AN XY:
686580
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.000184 AC: 28AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74494
GnomAD4 genome
AF:
AC:
28
AN:
152352
Hom.:
Cov.:
33
AF XY:
AC XY:
17
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
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. - |
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at