Variant 10-88817894-C-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.1000C>G(p.Gln334Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000215 in 1,397,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LIPM
NM_001128215.1 missense, splice_region

Scores

Splicing: ADA: 0.9285

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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=0.38747722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPM	NM_001128215.1 linkuse as main transcript	c.1000C>G	p.Gln334Glu	missense_variant, splice_region_variant	8/9	ENST00000404743.9
LIPM	XM_011539748.4 linkuse as main transcript	c.1021C>G	p.Gln341Glu	missense_variant, splice_region_variant	8/9
LIPM	XM_011539751.4 linkuse as main transcript	c.637C>G	p.Gln213Glu	missense_variant, splice_region_variant	7/8
LIPM	XM_011539752.4 linkuse as main transcript	c.451C>G	p.Gln151Glu	missense_variant, splice_region_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9 linkuse as main transcript	c.1000C>G	p.Gln334Glu	missense_variant, splice_region_variant	8/9	1	NM_001128215.1	P1	Q5VYY2-1
LIPM	ENST00000539337.2 linkuse as main transcript	c.880C>G	p.Gln294Glu	missense_variant, splice_region_variant	8/9	2			Q5VYY2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397782

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689492

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:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 14, 2023

The c.1000C>G (p.Q334E) alteration is located in exon 8 (coding exon 8) of the LIPM gene. This alteration results from a C to G substitution at nucleotide position 1000, causing the glutamine (Q) at amino acid position 334 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.39

T;T

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.8

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.88

P;.

Vest4

0.28

MutPred

0.64

Gain of disorder (P = 0.0678);.;

MVP

0.74

MPC

0.0037

ClinPred

0.98

GERP RS

5.8

Varity_R

0.63

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Benign

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over