rs748571081

Variant names:

• chr3-185514507-C-G
• rs748571081
• NM_139248.3:c.997G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-185514507-C-G
• chr3-185514507-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139248.3(LIPH):​c.997G>C​(p.Val333Leu) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V333M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPH NM_139248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

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]

LIPH Gene-Disease associations (from GenCC):

• hypotrichosis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TMEM41A-DT (HGNC:58335):

ENSG00000309120 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1848863).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139248.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPH	NM_139248.3	MANE Select	c.997G>C	p.Val333Leu	missense	Exon 8 of 10	NP_640341.1	Q8WWY8
	LIPH	NM_001438651.1		c.907G>C	p.Val303Leu	missense	Exon 7 of 9	NP_001425580.1
	LIPH	NM_001438029.1		c.895G>C	p.Val299Leu	missense	Exon 7 of 9	NP_001424958.1	A2IBA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPH	ENST00000296252.9	TSL:1 MANE Select	c.997G>C	p.Val333Leu	missense	Exon 8 of 10	ENSP00000296252.4	Q8WWY8
	LIPH	ENST00000424591.6	TSL:1	c.895G>C	p.Val299Leu	missense	Exon 7 of 9	ENSP00000396384.2	A2IBA6
	LIPH	ENST00000953488.1		c.1018G>C	p.Val340Leu	missense	Exon 8 of 10	ENSP00000623547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.28
Sift	Benign	0.73	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.57		Loss of MoRF binding (P = 0.1392)
MVP		0.78
MPC		0.13
ClinPred		0.24	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.78
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs748571081; hg19: chr3-185232295;