10-88814573-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001128215.1(LIPM):c.508T>C(p.Phe170Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000786 in 1,399,584 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: LIPM NM_001128215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPM	NM_001128215.1	c.508T>C	p.Phe170Leu	missense_variant	4/9	ENST00000404743.9
LIPM	XM_011539748.4	c.508T>C	p.Phe170Leu	missense_variant	4/9
LIPM	XM_011539751.4	c.124T>C	p.Phe42Leu	missense_variant	3/8
LIPM	XM_011539752.4	c.-51-12T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9	c.508T>C	p.Phe170Leu	missense_variant	4/9	1	NM_001128215.1	P1
LIPM	ENST00000539337.2	c.388T>C	p.Phe130Leu	missense_variant	4/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000786 AC: 11 AN: 1399584 Hom.: 0 Cov.: 31 AF XY: 0.00000579 AC XY: 4 AN XY: 690284

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: 0.0000102

Gnomad4 OTH exome AF: 0.00

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

Jan 10, 2023

The c.508T>C (p.F170L) alteration is located in exon 4 (coding exon 4) of the LIPM gene. This alteration results from a T to C substitution at nucleotide position 508, causing the phenylalanine (F) at amino acid position 170 to be replaced by a leucine (L). 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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.086	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.066	T;T
Sift4G	Uncertain	0.054	T;T
Polyphen		1.0	D;.
Vest4		0.65
MutPred		0.68		Loss of methylation at K174 (P = 0.0844);.;
MVP		0.61
MPC		0.0032
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.67
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90574330;