NM_005357.4:c.3221G>C

Variant names:

• chr19-42401822-C-G
• rs201301144
• NM_005357.4:c.3221G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005357.4(LIPE):​c.3221G>C​(p.Gly1074Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,477,752 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.38
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00436604).
• BP6: Variant 19-42401822-C-G is Benign according to our data. Variant chr19-42401822-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2650042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.3221G>C	p.Gly1074Ala	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2471G>C	p.Gly824Ala	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2456G>C	p.Gly819Ala	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.3221G>C	p.Gly1074Ala	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4598C>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3245G>C	p.Gly1082Ala	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 372 AN: 151734 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.00698

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.00317 AC: 266 AN: 83822 AF XY: 0.00351

Gnomad AFR exome AF: 0.000306

Gnomad AMR exome AF: 0.000200

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00902

Gnomad NFE exome AF: 0.00488

Gnomad OTH exome AF: 0.00292

GnomAD4 exome AF: 0.00281 AC: 3731 AN: 1325906 Hom.: 8 Cov.: 30 AF XY: 0.00273 AC XY: 1781 AN XY: 651486

African (AFR) AF: 0.000505 AC: 14 AN: 27718

American (AMR) AF: 0.000611 AC: 16 AN: 26202

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 49 AN: 21020

East Asian (EAS) AF: 0.00 AC: 0 AN: 33444

South Asian (SAS) AF: 0.00156 AC: 109 AN: 69934

European-Finnish (FIN) AF: 0.00754 AC: 305 AN: 40438

Middle Eastern (MID) AF: 0.000528 AC: 2 AN: 3790

European-Non Finnish (NFE) AF: 0.00297 AC: 3109 AN: 1048322

Other (OTH) AF: 0.00231 AC: 127 AN: 55038

GnomAD4 genome AF: 0.00245 AC: 372 AN: 151846 Hom.: 0 Cov.: 30 AF XY: 0.00268 AC XY: 199 AN XY: 74220

African (AFR) AF: 0.000845 AC: 35 AN: 41442

American (AMR) AF: 0.000786 AC: 12 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00232 AC: 8 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4796

European-Finnish (FIN) AF: 0.00698 AC: 74 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00339 AC: 230 AN: 67866

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.00258 Hom.: 1

Bravo AF: 0.00194

ExAC AF: 0.00241 AC: 212

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	LIPE-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.057
Sift	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.12
MVP		0.55
MPC		0.33
ClinPred		0.039	T
GERP RS		2.4
Varity_R		0.062
gMVP		0.20
Mutation Taster		=99/1	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: rs201301144; hg19: chr19-42905974;