chr9-136673513-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_006412.4(AGPAT2):c.*239G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 412,886 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 36 hom., cov: 34)
Exomes 𝑓: 0.0028 ( 10 hom. )
Consequence
AGPAT2
NM_006412.4 3_prime_UTR
NM_006412.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.36
Genes affected
AGPAT2 (HGNC:325): (1-acylglycerol-3-phosphate O-acyltransferase 2) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. The protein is located within the endoplasmic reticulum membrane and converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. Mutations in this gene have been associated with congenital generalized lipodystrophy (CGL), or Berardinelli-Seip syndrome, a disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 9-136673513-C-T is Benign according to our data. Variant chr9-136673513-C-T is described in ClinVar as [Benign]. Clinvar id is 365907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1880/152090) while in subpopulation AFR AF= 0.0392 (1629/41554). AF 95% confidence interval is 0.0376. There are 36 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 36 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGPAT2 | NM_006412.4 | c.*239G>A | 3_prime_UTR_variant | 6/6 | ENST00000371696.7 | ||
AGPAT2 | NM_001012727.2 | c.*239G>A | 3_prime_UTR_variant | 5/5 | |||
AGPAT2 | XM_047422636.1 | c.*239G>A | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGPAT2 | ENST00000371696.7 | c.*239G>A | 3_prime_UTR_variant | 6/6 | 1 | NM_006412.4 | P1 | ||
AGPAT2 | ENST00000371694.7 | c.*239G>A | 3_prime_UTR_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0123 AC: 1872AN: 151972Hom.: 36 Cov.: 34
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GnomAD4 exome AF: 0.00285 AC: 743AN: 260796Hom.: 10 Cov.: 4 AF XY: 0.00263 AC XY: 352AN XY: 133764
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GnomAD4 genome AF: 0.0124 AC: 1880AN: 152090Hom.: 36 Cov.: 34 AF XY: 0.0122 AC XY: 909AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Congenital generalized lipodystrophy type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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