2-11713787-G-T

Position:

• chr2-11713787-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001261428.3(LPIN1):​c.113G>T​(p.Arg38Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000732 in 1,365,216 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: LPIN1 NM_001261428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

Genes affected

LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.113G>T	p.Arg38Leu	missense_variant	2/22		NP_001248357.1
LPIN1	NM_001349208.2	c.113G>T	p.Arg38Leu	missense_variant	2/21		NP_001336137.1
LPIN1	NM_001349207.2	c.81+36059G>T		intron_variant			NP_001336136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.113G>T	p.Arg38Leu	missense_variant	2/22	2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000789 AC: 1 AN: 126740 Hom.: 0 AF XY: 0.0000144 AC XY: 1 AN XY: 69360

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000212

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1365216 Hom.: 0 Cov.: 27 AF XY: 0.00000148 AC XY: 1 AN XY: 674534

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.41e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.47	D
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.050	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.61
MutPred		0.44		Loss of MoRF binding (P = 0.0261);
MVP		0.76
MPC		0.42
ClinPred		0.66	D
GERP RS		4.9
gMVP		0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4614906; hg19: chr2-11853913;