Genetic Variant CLPSL2:p.Leu19Phe (chr6-35776673-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207409.4(CLPSL2):c.55C>T(p.Leu19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,472,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CLPSL2
NM_207409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.886

Publications

0 publications found

Variant links:

Genes affected

CLPSL2 (HGNC:21250): (colipase like 2) Predicted to enable enzyme activator activity. Predicted to be involved in response to food. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CLPSL2 links:

ENSG00000307849 (HGNC:):

ENSG00000307849 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035030544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPSL2	NM_207409.4	MANE Select	c.55C>T	p.Leu19Phe	missense	Exon 1 of 3	NP_997292.2	Q6UWE3-1
CLPSL2	NM_001286550.2		c.55C>T	p.Leu19Phe	missense	Exon 1 of 4	NP_001273479.1	Q6UWE3-2
CLPSL2	NR_104467.2		n.76C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPSL2	ENST00000403376.4	TSL:1 MANE Select	c.55C>T	p.Leu19Phe	missense	Exon 1 of 3	ENSP00000385898.3	Q6UWE3-1
CLPSL2	ENST00000360454.6	TSL:1	c.55C>T	p.Leu19Phe	missense	Exon 1 of 4	ENSP00000353639.2	Q6UWE3-2
CLPSL2	ENST00000924056.1		c.55C>T	p.Leu19Phe	missense	Exon 1 of 2	ENSP00000594115.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000271

AC:

AN:

73892

AF XY:

0.0000234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000136

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:

0.0000159

AC:

AN:

1320664

Hom.:

Cov.:

AF XY:

0.0000123

AC XY:

AN XY:

650086

show subpopulations

African (AFR)

AF:

0.000567

AC:

AN:

26462

American (AMR)

AF:

0.000113

AC:

AN:

26490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22824

East Asian (EAS)

AF:

0.00

AC:

AN:

29218

South Asian (SAS)

AF:

0.00

AC:

AN:

72662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32670

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051784

Other (OTH)

AF:

0.0000549

AC:

AN:

54666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41466

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.0000712

Hom.:

Bravo

AF:

0.000215

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.67

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.013

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.40

M_CAP

Benign

0.0020

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.89

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.039

Sift

Benign

0.049

Sift4G

Benign

0.082

Polyphen

0.047

Vest4

0.069

MutPred

0.17

Loss of helix (P = 0.1299)

MVP

0.014

MPC

0.066

ClinPred

0.026

GERP RS

-1.5

PromoterAI

0.055

Neutral

(source)

Varity_R

0.051

gMVP

0.059

Mutation Taster

=99/1

polymorphism

(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

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