Variant 10-88816838-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000404743.9(LIPM):c.881C>G(p.Ala294Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,551,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

LIPM
ENST00000404743.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10786393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIPM	NM_001128215.1 linkuse as main transcript	c.881C>G	p.Ala294Gly	missense_variant	7/9	ENST00000404743.9	NP_001121687.1
LIPM	XM_011539748.4 linkuse as main transcript	c.902C>G	p.Ala301Gly	missense_variant	7/9		XP_011538050.1
LIPM	XM_011539751.4 linkuse as main transcript	c.518C>G	p.Ala173Gly	missense_variant	6/8		XP_011538053.1
LIPM	XM_011539752.4 linkuse as main transcript	c.332C>G	p.Ala111Gly	missense_variant	5/7		XP_011538054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPM	ENST00000404743.9 linkuse as main transcript	c.881C>G	p.Ala294Gly	missense_variant	7/9	1	NM_001128215.1	ENSP00000383901	P1	Q5VYY2-1
LIPM	ENST00000539337.2 linkuse as main transcript	c.761C>G	p.Ala254Gly	missense_variant	7/9	2		ENSP00000440375		Q5VYY2-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

156504

Hom.:

AF XY:

0.0000482

AC XY:

AN XY:

82944

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1399078

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

690058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000789

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

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

Jan 17, 2024

The c.881C>G (p.A294G) alteration is located in exon 7 (coding exon 7) of the LIPM gene. This alteration results from a C to G substitution at nucleotide position 881, causing the alanine (A) at amino acid position 294 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0058

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.85

L;.

MutationTaster

Benign

0.80

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.095

Sift

Benign

0.36

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.055

B;.

Vest4

0.18

MutPred

0.64

Loss of stability (P = 0.017);.;

MVP

0.39

MPC

0.0028

ClinPred

0.095

GERP RS

5.5

Varity_R

0.20

gMVP

0.58

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