rs202243723

Variant names:

• chr8-48731379-A-C
• rs202243723
• NM_024593.4:c.183T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024593.4(CLXN):​c.183T>G​(p.Phe61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,612,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: CLXN NM_024593.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783
• Publications: 0 publications found

Genes affected

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

CLXN Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 53

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024593.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLXN	NM_024593.4	MANE Select	c.183T>G	p.Phe61Leu	missense	Exon 2 of 6	NP_078869.1	Q9HAE3-1
	CLXN	NM_001142857.2		c.59-735T>G		intron	N/A	NP_001136329.1	Q9HAE3-2
	CLXN	NM_001363973.3		c.59-735T>G		intron	N/A	NP_001350902.1	Q9HAE3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLXN	ENST00000262103.8	TSL:1 MANE Select	c.183T>G	p.Phe61Leu	missense	Exon 2 of 6	ENSP00000262103.3	Q9HAE3-1
	CLXN	ENST00000521002.5	TSL:1	n.292-2267T>G		intron	N/A
	CLXN	ENST00000521701.5	TSL:1	n.59-735T>G		intron	N/A	ENSP00000430374.1	H9KVD9

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000320 AC: 8 AN: 250386 AF XY: 0.0000443

Gnomad AFR exome AF: 0.000124

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: 0.0000530

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1460788 Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34 AN XY: 726694

African (AFR) AF: 0.0000299 AC: 1 AN: 33410

American (AMR) AF: 0.0000224 AC: 1 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000603 AC: 67 AN: 1111486

Other (OTH) AF: 0.0000331 AC: 2 AN: 60340

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74240

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.78
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.61
Sift	Benign	0.074	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.52		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.77
MPC		0.11
ClinPred		0.87	D
GERP RS		3.5
Varity_R		0.52
gMVP		0.56
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202243723; hg19: chr8-49643938;