NM_006412.4:c.*517C>T

Variant names:

• chr9-136673235-G-A
• rs10320
• NM_006412.4:c.*517C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006412.4(AGPAT2):​c.*517C>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 0.237 in 152,966 control chromosomes in the GnomAD database, including 4,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4832 hom., cov: 34)
  • Exomes 𝑓: 0.19 (21 hom.)
• Consequence: AGPAT2 NM_006412.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.46
• Publications: 6 publications found

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]

AGPAT2 Gene-Disease associations (from GenCC):

• congenital generalized lipodystrophy type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• lipodystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neonatal diabetes mellitus

  Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-136673235-G-A is Benign according to our data. Variant chr9-136673235-G-A is described in ClinVar as Benign. ClinVar VariationId is 365901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006412.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT2	NM_006412.4	MANE Select	c.*517C>T		3_prime_UTR	Exon 6 of 6	NP_006403.2
	AGPAT2	NM_001012727.2		c.*517C>T		3_prime_UTR	Exon 5 of 5	NP_001012745.1	O15120-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT2	ENST00000371696.7	TSL:1 MANE Select	c.*517C>T		3_prime_UTR	Exon 6 of 6	ENSP00000360761.2	O15120-1
	AGPAT2	ENST00000371694.7	TSL:1	c.*517C>T		3_prime_UTR	Exon 5 of 5	ENSP00000360759.3	O15120-2
	AGPAT2	ENST00000951406.1		c.*517C>T		3_prime_UTR	Exon 6 of 6	ENSP00000621465.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36083 AN: 152056 Hom.: 4815 Cov.: 34

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.192 AC: 152 AN: 792 Hom.: 21 Cov.: 0 AF XY: 0.196 AC XY: 88 AN XY: 450

African (AFR) AF: 0.235 AC: 8 AN: 34

American (AMR) AF: 0.0455 AC: 1 AN: 22

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 8 AN: 28

East Asian (EAS) AF: 0.679 AC: 19 AN: 28

South Asian (SAS) AF: 0.0714 AC: 1 AN: 14

European-Finnish (FIN) AF: 0.158 AC: 6 AN: 38

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.170 AC: 97 AN: 572

Other (OTH) AF: 0.240 AC: 12 AN: 50

GnomAD4 genome AF: 0.237 AC: 36119 AN: 152174 Hom.: 4832 Cov.: 34 AF XY: 0.241 AC XY: 17930 AN XY: 74390

African (AFR) AF: 0.217 AC: 9022 AN: 41528

American (AMR) AF: 0.268 AC: 4105 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3037 AN: 5168

South Asian (SAS) AF: 0.397 AC: 1917 AN: 4830

European-Finnish (FIN) AF: 0.228 AC: 2418 AN: 10602

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14089 AN: 67958

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.221 Hom.: 1602

Bravo AF: 0.241

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital generalized lipodystrophy type 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.54
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10320; hg19: chr9-139567687;