Genetic Variant LAP3:p.Leu4Leu (chr4-17577477-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_015907.3(LAP3):c.12G>C(p.Leu4Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,579,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LAP3
NM_015907.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

Publications

0 publications found

Variant links:

Genes affected

LAP3 (HGNC:18449): (leucine aminopeptidase 3) Predicted to enable peptidase activity. Predicted to be involved in proteolysis. Located in cytosol; midbody; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LAP3 links:

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new If you want to explore the variant's impact on the transcript NM_015907.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=2.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015907.3. 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
	LAP3	NM_015907.3	MANE Select	c.12G>C	p.Leu4Leu	synonymous	Exon 1 of 13	NP_056991.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAP3	ENST00000226299.9	TSL:1 MANE Select	c.12G>C	p.Leu4Leu	synonymous	Exon 1 of 13	ENSP00000226299.4	P28838-1
LAP3	ENST00000618908.4	TSL:1	c.12G>C	p.Leu4Leu	synonymous	Exon 1 of 13	ENSP00000481000.1	P28838-1
LAP3	ENST00000955710.1		c.12G>C	p.Leu4Leu	synonymous	Exon 1 of 11	ENSP00000625769.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426924

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707328

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32200

American (AMR)

AF:

0.00

AC:

AN:

40198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

37636

South Asian (SAS)

AF:

0.00

AC:

AN:

81630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4168

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096404

Other (OTH)

AF:

0.0000170

AC:

AN:

58898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

2.9

PromoterAI

-0.20

Neutral

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over