21-14152684-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001302998.2(LIPI):c.1007C>G(p.Thr336Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict 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)
• Consequence: LIPI NM_001302998.2 missense, splice_region
• Scores: Splicing: ADA: 0.0009005
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

LIPI (HGNC:18821): (lipase I) The protein encoded by this gene is a phospholipase that hydrolyzes phosphatidic acid to produce lysophosphatidic acid. Defects in this gene are a cause of susceptibility to familial hypertrigliceridemia. This gene is also expressed at high levels in Ewing family tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

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=0.23489764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.1007C>G	p.Thr336Ser	missense_variant, splice_region_variant	8/10	ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.1007C>G	p.Thr336Ser	missense_variant, splice_region_variant	8/10		NM_001302998.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

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 23, 2024

The c.1070C>G (p.T357S) alteration is located in exon 8 (coding exon 8) of the LIPI gene. This alteration results from a C to G substitution at nucleotide position 1070, causing the threonine (T) at amino acid position 357 to be replaced by a serine (S). 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
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	16
Dann	Benign	0.97
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.43	T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.87	N;.;.
REVEL	Benign	0.26
Sift	Benign	0.40	T;.;.
Sift4G	Benign	0.80	T;T;T
Polyphen		0.082	B;.;.
Vest4		0.25
MutPred		0.53		Loss of sheet (P = 0.1158);.;.;
MVP		0.48
MPC		0.017
ClinPred		0.17	T
GERP RS		3.5
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00090
dbscSNV1_RF	Benign	0.17
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: chr21-15525005;