10-88602632-G-T

Position:

• chr10-88602632-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010939.3(LIPJ):​c.780G>T​(p.Met260Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000504 in 1,190,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: LIPJ NM_001010939.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.593

Genes affected

LIPJ (HGNC:21773): (lipase family member J) Predicted to enable hydrolase activity, acting on ester bonds. Predicted to be involved in lipid catabolic process. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047011405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPJ	NM_001010939.3	c.780G>T	p.Met260Ile	missense_variant	9/11	ENST00000371939.7	NP_001010939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPJ	ENST00000371939.7	c.780G>T	p.Met260Ile	missense_variant	9/11	1	NM_001010939.3	ENSP00000361007.3
LIPJ	ENST00000531458.1	c.225G>T	p.Met75Ile	missense_variant	3/5	3		ENSP00000434211.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000504 AC: 6 AN: 1190484 Hom.: 0 Cov.: 29 AF XY: 0.00000338 AC XY: 2 AN XY: 591934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000490

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000291

Gnomad4 NFE exome AF: 0.00000431

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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 15, 2021

The c.780G>T (p.M260I) alteration is located in exon 9 (coding exon 7) of the LIPJ gene. This alteration results from a G to T substitution at nucleotide position 780, causing the methionine (M) at amino acid position 260 to be replaced by an isoleucine (I). 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	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.74
DANN	Benign	0.30
DEOGEN2	Benign	0.0060	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.045	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.070
Sift	Benign	0.97	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.16
MutPred		0.63		Loss of disorder (P = 0.092);.;
MVP		0.29
MPC		0.037
ClinPred		0.036	T
GERP RS		-1.8
Varity_R		0.052
gMVP		0.50

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: chr10-90362389;