9-136673595-G-A

Position:

• chr9-136673595-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006412.4(AGPAT2):​c.*157C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 827,698 control chromosomes in the GnomAD database, including 284,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46763 hom., cov: 34)
  • Exomes 𝑓: 0.84 (237607 hom.)
• Consequence: AGPAT2 NM_006412.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0650

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-136673595-G-A is Benign according to our data. Variant chr9-136673595-G-A is described in ClinVar as [Benign]. Clinvar id is 365913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGPAT2	NM_006412.4	c.*157C>T		3_prime_UTR_variant	6/6	ENST00000371696.7
AGPAT2	NM_001012727.2	c.*157C>T		3_prime_UTR_variant	5/5
AGPAT2	XM_047422636.1	c.*157C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGPAT2	ENST00000371696.7	c.*157C>T		3_prime_UTR_variant	6/6	1	NM_006412.4	P1
AGPAT2	ENST00000371694.7	c.*157C>T		3_prime_UTR_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118144 AN: 152010 Hom.: 46770 Cov.: 34

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.837 AC: 565654 AN: 675570 Hom.: 237607 Cov.: 9 AF XY: 0.839 AC XY: 283784 AN XY: 338252

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.849

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.777 AC: 118165 AN: 152128 Hom.: 46763 Cov.: 34 AF XY: 0.780 AC XY: 58030 AN XY: 74376

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.762

Alfa AF: 0.817 Hom.: 43300

Bravo AF: 0.765

Asia WGS AF: 0.885 AC: 3080 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital generalized lipodystrophy type 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, 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 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4880119; hg19: chr9-139568047; COSMIC: COSV58248920; COSMIC: COSV58248920;