8-48729844-C-A

Variant names:

• chr8-48729844-C-A
• rs1585546659
• NM_024593.4:c.347G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024593.4(CLXN):​c.347G>T​(p.Gly116Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLXN NM_024593.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• 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

ENSG00000253608 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

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.347G>T	p.Gly116Val	missense	Exon 4 of 6	NP_078869.1	Q9HAE3-1
	CLXN	NM_001142857.2		c.191G>T	p.Gly64Val	missense	Exon 3 of 6	NP_001136329.1	Q9HAE3-2
	CLXN	NM_001363973.3		c.191G>T	p.Gly64Val	missense	Exon 3 of 6	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.347G>T	p.Gly116Val	missense	Exon 4 of 6	ENSP00000262103.3	Q9HAE3-1
	CLXN	ENST00000521002.5	TSL:1	n.292-732G>T		intron	N/A
	CLXN	ENST00000521701.5	TSL:1	n.164-20G>T		intron	N/A	ENSP00000430374.1	H9KVD9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.67
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		3.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Polyphen		0.95	P
Vest4		0.65
MutPred		0.63		Loss of disorder (P = 0.0659)
MVP		0.92
MPC		0.30
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		-0.00020	Neutral
Varity_R		0.88
gMVP		0.72
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -20

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

Other links and lift over

dbSNP: rs1585546659; hg19: chr8-49642403;