Variant 6-35779371-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_207409.4(CLPSL2):c.224A>G(p.Asn75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,575,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

CLPSL2
NM_207409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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:

CLPSL2 (HGNC:):

CLPSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3159976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPSL2	NM_207409.4 linkuse as main transcript	c.224A>G	p.Asn75Ser	missense_variant	3/3	ENST00000403376.4	NP_997292.2	Q6UWE3-1
CLPSL2	NM_001286550.2 linkuse as main transcript	c.303A>G	p.Gln101Gln	synonymous_variant	4/4		NP_001273479.1	Q6UWE3-2
CLPSL2	NR_104467.2 linkuse as main transcript	n.347A>G		non_coding_transcript_exon_variant	3/3
CLPSL2	NR_104469.2 linkuse as main transcript	n.224A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLPSL2	ENST00000403376.4 linkuse as main transcript	c.224A>G	p.Asn75Ser	missense_variant	3/3	1	NM_207409.4	ENSP00000385898.3	Q6UWE3-1
CLPSL2	ENST00000360454.6 linkuse as main transcript	c.303A>G	p.Gln101Gln	synonymous_variant	4/4	1		ENSP00000353639.2	Q6UWE3-2
CLPSL2	ENST00000467122.1 linkuse as main transcript	n.132A>G		non_coding_transcript_exon_variant	2/2	3
CLPSL2	ENST00000481904.5 linkuse as main transcript	n.351A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1423468

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703242

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:

0.00000734

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

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

May 23, 2023

The c.224A>G (p.N75S) alteration is located in exon 3 (coding exon 3) of the CLPSL2 gene. This alteration results from a A to G substitution at nucleotide position 224, causing the asparagine (N) at amino acid position 75 to be replaced by a serine (S). 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

Benign

0.32

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

Eigen

Benign

0.15

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.62

M_CAP

Benign

0.0054

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.096

Sift

Uncertain

0.024

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.42

MutPred

0.36

Gain of disorder (P = 0.0566);

MVP

0.17

MPC

0.053

ClinPred

0.41

GERP RS

2.7

Varity_R

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over