6-35787903-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001010886.5(CLPSL1):​c.259C>T​(p.Arg87Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,606,962 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 40)
Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

CLPSL1
NM_001010886.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.315
Variant links:
Genes affected
CLPSL1 (HGNC:21251): (colipase like 1) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04101321).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLPSL1NM_001010886.5 linkc.259C>T p.Arg87Trp missense_variant Exon 3 of 3 ENST00000373861.6 NP_001010886.1
CLPSL1XM_017010820.2 linkc.271C>T p.Arg91Trp missense_variant Exon 2 of 2 XP_016866309.1
CLPSL1NM_001348773.2 linkc.222+783C>T intron_variant Intron 2 of 2 NP_001335702.1
CLPSL1XM_017010821.2 linkc.234+783C>T intron_variant Intron 1 of 1 XP_016866310.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLPSL1ENST00000373861.6 linkc.259C>T p.Arg87Trp missense_variant Exon 3 of 3 1 NM_001010886.5 ENSP00000362968.5 A2RUU4
CLPSL1ENST00000428710.1 linkc.81+783C>T intron_variant Intron 1 of 1 3 ENSP00000396556.1 Q5T9G0

Frequencies

GnomAD3 genomes
AF:
0.000144
AC:
22
AN:
152258
Hom.:
0
Cov.:
40
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000232
AC:
58
AN:
249550
Hom.:
0
AF XY:
0.000295
AC XY:
40
AN XY:
135398
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.000948
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000180
AC:
262
AN:
1454704
Hom.:
2
Cov.:
32
AF XY:
0.000210
AC XY:
152
AN XY:
724092
show subpopulations
Gnomad4 AFR exome
AF:
0.0000900
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00110
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000941
Gnomad4 OTH exome
AF:
0.000665
GnomAD4 genome
AF:
0.000144
AC:
22
AN:
152258
Hom.:
0
Cov.:
40
AF XY:
0.000148
AC XY:
11
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00103
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
0
ESP6500AA
AF:
0.000247
AC:
1
ESP6500EA
AF:
0.000119
AC:
1
ExAC
AF:
0.000198
AC:
24
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.259C>T (p.R87W) alteration is located in exon 3 (coding exon 3) of the CLPSL1 gene. This alteration results from a C to T substitution at nucleotide position 259, causing the arginine (R) at amino acid position 87 to be replaced by a tryptophan (W). 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
0.092
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.041
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-4.6
D
REVEL
Benign
0.10
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.013
D
Polyphen
0.99
D
Vest4
0.13
MVP
0.17
MPC
0.021
ClinPred
0.089
T
GERP RS
0.81
Varity_R
0.086
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs201083630; hg19: chr6-35755680; API