8-48729117-A-T

Variant names:

• chr8-48729117-A-T
• NM_024593.4:c.501T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024593.4(CLXN):​c.501T>A​(p.Phe167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.38

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLXN	NM_024593.4	c.501T>A	p.Phe167Leu	missense_variant	Exon 5 of 6	ENST00000262103.8	NP_078869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLXN	ENST00000262103.8	c.501T>A	p.Phe167Leu	missense_variant	Exon 5 of 6	1	NM_024593.4	ENSP00000262103.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.501T>A (p.F167L) alteration is located in exon 5 (coding exon 5) of the EFCAB1 gene. This alteration results from a T to A substitution at nucleotide position 501, causing the phenylalanine (F) at amino acid position 167 to be replaced by a leucine (L). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.36	.;T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T;T;.
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	.;N;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.71
MutPred		0.50		.;Loss of catalytic residue at F167 (P = 0.0648);.;
MVP		0.70
MPC		0.052
ClinPred		0.47	T
GERP RS		1.8
Varity_R		0.24
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-49641676;