rs149564563

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PP3_ModerateBP3BP6_Very_StrongBS1BS2

The NM_001349206.2(LPIN1):c.964_966delTCT(p.Ser322del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,014 control chromosomes in the GnomAD database, including 44 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

LPIN1
NM_001349206.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.10

Variant links:

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]

LPIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP3

Nonframeshift variant in repetitive region in NM_001349206.2

BP6

Variant 2-11782200-GTCT-G is Benign according to our data. Variant chr2-11782200-GTCT-G is described in ClinVar as [Likely_benign]. Clinvar id is 262597.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 = 0.0102 (1556/152188) while in subpopulation AFR AF= 0.0352 (1462/41502). AF 95% confidence interval is 0.0337. There are 24 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2 link	c.964_966delTCT	p.Ser322del	conservative_inframe_deletion	Exon 8 of 21	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1 link	c.964_966delTCT	p.Ser322del	conservative_inframe_deletion	Exon 8 of 21		NM_001349206.2	ENSP00000501331.1		Q14693-3

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1554

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00238

AC:

595

AN:

250492

Hom.:

AF XY:

0.00181

AC XY:

246

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.0339

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00103

AC:

1504

AN:

1460826

Hom.:

AF XY:

0.000890

AC XY:

647

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.0387

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.0102

AC:

1556

AN:

152188

Hom.:

Cov.:

AF XY:

0.00978

AC XY:

728

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22481384) -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myoglobinuria, acute recurrent, autosomal recessive

Benign:1

Jan 13, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Acute Recurrent Myoglobinuria

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.98

Position offset: 4

DS_AL_spliceai

0.98

Position offset: 1

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