rs201249971

Variant names:

• chr3-185519292-A-G
• NM_139248.3:c.736T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-185519292-A-G
• chr3-185519292-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_139248.3(LIPH):​c.736T>C​(p.Cys246Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIPH NM_139248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.09

Genes affected

LIPH (HGNC:18483): (lipase H) This gene encodes a membrane-bound member of the mammalian triglyceride lipase family. It catalyzes the production of 2-acyl lysophosphatidic acid (LPA), which is a lipid mediator with diverse biological properties that include platelet aggregation, smooth muscle contraction, and stimulation of cell proliferation and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.995

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPH	NM_139248.3	c.736T>C	p.Cys246Arg	missense_variant	Exon 6 of 10	ENST00000296252.9	NP_640341.1
LIPH	XM_006713529.5	c.646T>C	p.Cys216Arg	missense_variant	Exon 5 of 9		XP_006713592.1
LIPH	XM_017005852.3	c.634T>C	p.Cys212Arg	missense_variant	Exon 5 of 9		XP_016861341.1
LIPH	XM_011512530.4	c.607T>C	p.Cys203Arg	missense_variant	Exon 7 of 11		XP_011510832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPH	ENST00000296252.9	c.736T>C	p.Cys246Arg	missense_variant	Exon 6 of 10	1	NM_139248.3	ENSP00000296252.4
LIPH	ENST00000424591.6	c.634T>C	p.Cys212Arg	missense_variant	Exon 5 of 9	1		ENSP00000396384.2
LIPH	ENST00000452897.1	c.106T>C	p.Cys36Arg	missense_variant	Exon 2 of 2	3		ENSP00000408218.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460778 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726800

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D;D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.8	H;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-11	D;D
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		1.0
MutPred		0.97		Loss of methylation at K245 (P = 0.0318);.;
MVP		0.98
MPC		0.77
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.97
gMVP		1.0

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: chr3-185237080;