NM_139248.3:c.*86G>A

Variant names:

• chr3-185508704-C-T
• rs55854644
• NM_139248.3:c.*86G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139248.3(LIPH):​c.*86G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 972,864 control chromosomes in the GnomAD database, including 34,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4057 hom., cov: 33)
  • Exomes 𝑓: 0.26 (30702 hom.)
• Consequence: LIPH NM_139248.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.815
• Publications: 5 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-185508704-C-T is Benign according to our data. Variant chr3-185508704-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

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.*86G>A		3_prime_UTR	Exon 10 of 10	NP_640341.1	Q8WWY8
	LIPH	NM_001438651.1		c.*86G>A		3_prime_UTR	Exon 9 of 9	NP_001425580.1
	LIPH	NM_001438029.1		c.*86G>A		3_prime_UTR	Exon 9 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.*86G>A		3_prime_UTR	Exon 10 of 10	ENSP00000296252.4	Q8WWY8
	LIPH	ENST00000424591.6	TSL:1	c.*86G>A		3_prime_UTR	Exon 9 of 9	ENSP00000396384.2	A2IBA6
	LIPH	ENST00000953488.1		c.*86G>A		3_prime_UTR	Exon 10 of 10	ENSP00000623547.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30628 AN: 152056 Hom.: 4058 Cov.: 33

Gnomad AFR AF: 0.0523

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.258 AC: 211975 AN: 820690 Hom.: 30702 Cov.: 11 AF XY: 0.257 AC XY: 111371 AN XY: 432516

African (AFR) AF: 0.0457 AC: 966 AN: 21148

American (AMR) AF: 0.128 AC: 5278 AN: 41080

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 6783 AN: 21856

East Asian (EAS) AF: 0.000708 AC: 26 AN: 36704

South Asian (SAS) AF: 0.196 AC: 14049 AN: 71594

European-Finnish (FIN) AF: 0.277 AC: 14501 AN: 52318

Middle Eastern (MID) AF: 0.278 AC: 1264 AN: 4540

European-Non Finnish (NFE) AF: 0.299 AC: 159270 AN: 531924

Other (OTH) AF: 0.249 AC: 9838 AN: 39526

GnomAD4 genome AF: 0.201 AC: 30622 AN: 152174 Hom.: 4057 Cov.: 33 AF XY: 0.198 AC XY: 14694 AN XY: 74378

African (AFR) AF: 0.0521 AC: 2167 AN: 41560

American (AMR) AF: 0.169 AC: 2578 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1005 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5174

South Asian (SAS) AF: 0.192 AC: 925 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2886 AN: 10570

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20278 AN: 67982

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.269 Hom.: 1232

Bravo AF: 0.187

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.8
DANN	Benign	0.61
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs55854644; hg19: chr3-185226492; COSMIC: COSV56183594;