rs766485323

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024593.4(CLXN):​c.293G>T​(p.Arg98Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R98Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CLXN
NM_024593.4 missense

Scores

8
9
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.08
Variant links:
Genes affected
CLXN (HGNC:25678): (calaxin) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLXNNM_024593.4 linkc.293G>T p.Arg98Leu missense_variant Exon 3 of 6 ENST00000262103.8 NP_078869.1 Q9HAE3-1A0A024R7U5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLXNENST00000262103.8 linkc.293G>T p.Arg98Leu missense_variant Exon 3 of 6 1 NM_024593.4 ENSP00000262103.3 Q9HAE3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248674
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134520
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000466
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458090
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725432
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:
0.0000188
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T;.
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D;.
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Uncertain
0.29
D
MutationAssessor
Uncertain
2.3
.;M;.
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-6.5
D;D;D
REVEL
Uncertain
0.57
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.010
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.95
MutPred
0.47
.;Loss of phosphorylation at S100 (P = 0.0616);.;
MVP
0.94
MPC
0.24
ClinPred
1.0
D
GERP RS
4.4
Varity_R
0.68
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.57
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: -3
DS_DL_spliceai
0.57
Position offset: -26

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: rs766485323; hg19: chr8-49643125; COSMIC: COSV100030834; COSMIC: COSV100030834; API