NM_005357.4:c.3169G>C

Variant names:

• chr19-42401874-C-G
• rs1161696034
• NM_005357.4:c.3169G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_005357.4(LIPE):​c.3169G>C​(p.Ala1057Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000724 in 1,380,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.405
• Publications: 1 publications found

Genes affected

LIPE (HGNC:6621): (lipase E, hormone sensitive type) The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids. [provided by RefSeq, Jul 2008]

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LOC101930071 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09145743).
• BP6: Variant 19-42401874-C-G is Benign according to our data. Variant chr19-42401874-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3538458.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005357.4. 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
	LIPE	NM_005357.4	MANE Select	c.3169G>C	p.Ala1057Pro	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2419G>C	p.Ala807Pro	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2404G>C	p.Ala802Pro	missense	Exon 10 of 10	NP_001403030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	ENST00000244289.9	TSL:1 MANE Select	c.3169G>C	p.Ala1057Pro	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4650C>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3193G>C	p.Ala1065Pro	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000154 AC: 2 AN: 129888 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000865

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000724 AC: 10 AN: 1380950 Hom.: 0 Cov.: 36 AF XY: 0.00000733 AC XY: 5 AN XY: 681734

African (AFR) AF: 0.00 AC: 0 AN: 30166

American (AMR) AF: 0.0000860 AC: 3 AN: 34892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24538

East Asian (EAS) AF: 0.00 AC: 0 AN: 34872

South Asian (SAS) AF: 0.00 AC: 0 AN: 77988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4278

European-Non Finnish (NFE) AF: 0.00000650 AC: 7 AN: 1077188

Other (OTH) AF: 0.00 AC: 0 AN: 57488

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Benign	0.70
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.090	N
PhyloP100		0.41
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.070
Sift	Benign	0.35	T
Sift4G	Benign	0.095	T
Polyphen		0.98	D
Vest4		0.083
MutPred		0.24		Gain of glycosylation at A1057 (P = 0.0046)
MVP		0.46
MPC		0.40
ClinPred		0.12	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.057
gMVP		0.15
Mutation Taster		=95/5	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: rs1161696034; hg19: chr19-42906026;