Variant 6-35777498-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207409.4(CLPSL2):c.124A>G(p.Ser42Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CLPSL2
NM_207409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLPSL2	NM_207409.4 linkuse as main transcript	c.124A>G	p.Ser42Gly	missense_variant	2/3	ENST00000403376.4	NP_997292.2
CLPSL2	NM_001286550.2 linkuse as main transcript	c.124A>G	p.Ser42Gly	missense_variant	2/4		NP_001273479.1
CLPSL2	NR_104467.2 linkuse as main transcript	n.247A>G		non_coding_transcript_exon_variant	2/3
CLPSL2	NR_104469.2 linkuse as main transcript	n.207+694A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPSL2	ENST00000403376.4 linkuse as main transcript	c.124A>G	p.Ser42Gly	missense_variant	2/3	1	NM_207409.4	ENSP00000385898	P1	Q6UWE3-1
CLPSL2	ENST00000360454.6 linkuse as main transcript	c.124A>G	p.Ser42Gly	missense_variant	2/4	1		ENSP00000353639		Q6UWE3-2
CLPSL2	ENST00000481904.5 linkuse as main transcript	n.251A>G		non_coding_transcript_exon_variant	2/3	3
CLPSL2	ENST00000467122.1 linkuse as main transcript	n.115+694A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461468

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.124A>G (p.S42G) alteration is located in exon 2 (coding exon 2) of the CLPSL2 gene. This alteration results from a A to G substitution at nucleotide position 124, causing the serine (S) at amino acid position 42 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

.;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

-0.0010

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0045

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.62

MutPred

0.24

Loss of glycosylation at S42 (P = 0.0578);Loss of glycosylation at S42 (P = 0.0578);

MVP

0.19

MPC

0.19

ClinPred

0.99

GERP RS

3.4

Varity_R

0.56

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over