Variant 10-88817891-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128215.1(LIPM):c.997A>G(p.Asn333Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000858 in 1,398,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

LIPM
NM_001128215.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.585

Variant links:

Genes affected

LIPM (HGNC:23455): (lipase family member M) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LIPM links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2997955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPM	NM_001128215.1 linkuse as main transcript	c.997A>G	p.Asn333Asp	missense_variant	8/9	ENST00000404743.9
LIPM	XM_011539748.4 linkuse as main transcript	c.1018A>G	p.Asn340Asp	missense_variant	8/9
LIPM	XM_011539751.4 linkuse as main transcript	c.634A>G	p.Asn212Asp	missense_variant	7/8
LIPM	XM_011539752.4 linkuse as main transcript	c.448A>G	p.Asn150Asp	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9 linkuse as main transcript	c.997A>G	p.Asn333Asp	missense_variant	8/9	1	NM_001128215.1	P1	Q5VYY2-1
LIPM	ENST00000539337.2 linkuse as main transcript	c.877A>G	p.Asn293Asp	missense_variant	8/9	2			Q5VYY2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000640

AC:

AN:

156294

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82830

show subpopulations

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:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1398512

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689818

show subpopulations

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:

0.0000111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.997A>G (p.N333D) alteration is located in exon 8 (coding exon 8) of the LIPM gene. This alteration results from a A to G substitution at nucleotide position 997, causing the asparagine (N) at amino acid position 333 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;.

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.52

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.30

T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.72

N;N

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.26

Sift

Benign

0.044

D;D

Sift4G

Uncertain

0.053

T;T

Polyphen

0.97

D;.

Vest4

0.33

MutPred

0.59

Loss of MoRF binding (P = 0.1185);.;

MVP

0.71

MPC

0.0024

ClinPred

0.91

GERP RS

4.7

Varity_R

0.36

gMVP

0.91

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