10-88817838-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001128215.1(LIPM):c.944G>T(p.Gly315Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPM NM_001128215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPM	NM_001128215.1	c.944G>T	p.Gly315Val	missense_variant	8/9	ENST00000404743.9
LIPM	XM_011539748.4	c.965G>T	p.Gly322Val	missense_variant	8/9
LIPM	XM_011539751.4	c.581G>T	p.Gly194Val	missense_variant	7/8
LIPM	XM_011539752.4	c.395G>T	p.Gly132Val	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9	c.944G>T	p.Gly315Val	missense_variant	8/9	1	NM_001128215.1	P1
LIPM	ENST00000539337.2	c.824G>T	p.Gly275Val	missense_variant	8/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.944G>T (p.G315V) alteration is located in exon 8 (coding exon 8) of the LIPM gene. This alteration results from a G to T substitution at nucleotide position 944, causing the glycine (G) at amino acid position 315 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	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
Cadd	Pathogenic	29
Dann	Uncertain	1.0
DEOGEN2	Benign	0.079	T;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Pathogenic	3.8	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.1	D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;.
Vest4		0.70
MutPred		0.71		Loss of relative solvent accessibility (P = 0.0404);.;
MVP		0.90
MPC		0.0054
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.89
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90577595;