Genetic Variant LIPM:p.Ala294Val (chr10-88816838-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001128215.1(LIPM):c.881C>T(p.Ala294Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000451 in 1,551,220 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A294G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

LIPM
NM_001128215.1 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4063354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPM	NM_001128215.1 link	c.881C>T	p.Ala294Val	missense_variant	Exon 7 of 9	ENST00000404743.9	NP_001121687.1	Q5VYY2-1
LIPM	XM_011539748.4 link	c.902C>T	p.Ala301Val	missense_variant	Exon 7 of 9		XP_011538050.1
LIPM	XM_011539751.4 link	c.518C>T	p.Ala173Val	missense_variant	Exon 6 of 8		XP_011538053.1
LIPM	XM_011539752.4 link	c.332C>T	p.Ala111Val	missense_variant	Exon 5 of 7		XP_011538054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPM	ENST00000404743.9 link	c.881C>T	p.Ala294Val	missense_variant	Exon 7 of 9	1	NM_001128215.1	ENSP00000383901.3		Q5VYY2-1
LIPM	ENST00000539337.2 link	c.761C>T	p.Ala254Val	missense_variant	Exon 7 of 9	2		ENSP00000440375.1		Q5VYY2-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1399078

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

690058

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:

0.00000556

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.881C>T (p.A294V) alteration is located in exon 7 (coding exon 7) of the LIPM gene. This alteration results from a C to T substitution at nucleotide position 881, causing the alanine (A) at amino acid position 294 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.41

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.95

P;.

Vest4

0.40

MutPred

0.60

Gain of sheet (P = 0.0827);.;

MVP

0.45

MPC

0.0052

ClinPred

0.98

GERP RS

5.5

Varity_R

0.50

gMVP

0.70

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