dbSNP rs139719161: CLPSL2:p.Arg81Trp (chr6-35779388-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207409.4(CLPSL2):c.241C>T(p.Arg81Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,584,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CLPSL2
NM_207409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.551

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.10581416).

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.241C>T	p.Arg81Trp	missense	Exon 3 of 3	NP_997292.2	Q6UWE3-1
CLPSL2	NM_001286550.2		c.320C>T	p.Pro107Leu	missense	Exon 4 of 4	NP_001273479.1	Q6UWE3-2
CLPSL2	NR_104467.2		n.364C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPSL2	ENST00000403376.4	TSL:1 MANE Select	c.241C>T	p.Arg81Trp	missense	Exon 3 of 3	ENSP00000385898.3	Q6UWE3-1
CLPSL2	ENST00000360454.6	TSL:1	c.320C>T	p.Pro107Leu	missense	Exon 4 of 4	ENSP00000353639.2	Q6UWE3-2
CLPSL2	ENST00000924056.1		c.118C>T	p.Arg40Trp	missense	Exon 2 of 2	ENSP00000594115.1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

209102

AF XY:

0.0000179

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1432108

Hom.:

Cov.:

AF XY:

0.00000987

AC XY:

AN XY:

709234

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32918

American (AMR)

AF:

0.00

AC:

AN:

40474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25536

East Asian (EAS)

AF:

0.0000520

AC:

AN:

38486

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00000821

AC:

AN:

1096192

Other (OTH)

AF:

0.00

AC:

AN:

59378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000854

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.000112

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

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

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.44

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

PhyloP100

0.55

PROVEAN

Benign

-0.63

REVEL

Benign

0.096

Sift

Pathogenic

0.0

Polyphen

1.0

Vest4

0.35

MVP

0.24

ClinPred

0.96

GERP RS

3.3

Varity_R

0.25

gMVP

0.16

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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