Variant 20-41345827-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_022896.3(LPIN3):c.24G>A(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,613,488 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 16 hom. )

Consequence

LPIN3
NM_022896.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.93

Variant links:

Genes affected

LPIN3 (HGNC:14451): (lipin 3) The protein encoded by this gene is a member of the lipin family of proteins, and all family members share strong homology in their C-terminal region. This protein is thought to form hetero-oligomers with other lipin family members, while one family member, lipin 1, can also form homo-oligomers. This protein contains conserved motifs for phosphatidate phosphatase 1 (PAP1) activity as well as a domain that interacts with a transcriptional co-activator. Lipin complexes act in the cytoplasm to catalyze the dephosphorylation of phosphatidic acid to produce diacylglycerol, which is the precursor of both triglycerides and phospholipids. Lipin complexes are also thought to regulate gene expression as transcriptional co-activators in the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

LPIN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 20-41345827-G-A is Benign according to our data. Variant chr20-41345827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652325.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN3	NM_022896.3 link	c.24G>A	p.Ala8Ala	synonymous_variant	2/20	ENST00000373257.8	NP_075047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN3	ENST00000373257.8 link	c.24G>A	p.Ala8Ala	synonymous_variant	2/20	5	NM_022896.3	ENSP00000362354.3		Q9BQK8-1
LPIN3	ENST00000632009.1 link	c.24G>A	p.Ala8Ala	synonymous_variant	2/20	1		ENSP00000487971.1		Q9BQK8-2

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00310

AC:

775

AN:

250366

Hom.:

AF XY:

0.00330

AC XY:

446

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00367

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00360

AC:

5258

AN:

1461136

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

2651

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00374

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00263

AC:

400

AN:

152352

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

182

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00344

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00485

EpiControl

AF:

0.00504

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

LPIN3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.41

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over