chr10-89214840-C-A

Variant names:

• chr10-89214840-C-A
• NM_000235.4:c.1188G>T

Variant summary

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

The NM_000235.4(LIPA):​c.1188G>T​(p.Arg396Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LIPA NM_000235.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309

Genes affected

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 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=0.15250549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_000235.4	c.1188G>T	p.Arg396Ser	missense_variant	Exon 10 of 10	ENST00000336233.10	NP_000226.2
LIPA	NM_001127605.3	c.1188G>T	p.Arg396Ser	missense_variant	Exon 10 of 10		NP_001121077.1
LIPA	NM_001288979.2	c.840G>T	p.Arg280Ser	missense_variant	Exon 8 of 8		NP_001275908.1
LIPA	XM_024448023.2	c.1188G>T	p.Arg396Ser	missense_variant	Exon 10 of 10		XP_024303791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.1188G>T	p.Arg396Ser	missense_variant	Exon 10 of 10	1	NM_000235.4	ENSP00000337354.5
LIPA	ENST00000371837.5	c.1020G>T	p.Arg340Ser	missense_variant	Exon 9 of 9	2		ENSP00000360903.1
LIPA	ENST00000456827.5	c.840G>T	p.Arg280Ser	missense_variant	Exon 8 of 8	3		ENSP00000413019.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436582 Hom.: 0 Cov.: 26 AF XY: 0.00000140 AC XY: 1 AN XY: 716370

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: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.076
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.078	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.084
MutPred		0.44		Loss of MoRF binding (P = 0.0568);.;.;
MVP		0.87
MPC		0.16
ClinPred		0.72	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.77

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: chr10-90974597; COSMIC: COSV60330319;