7-143382636-T-C

Position:

• chr7-143382636-T-C

Variant summary

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

The NM_003461.5(ZYX):​c.452T>C​(p.Leu151Pro) variant causes a missense change. 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: ZYX NM_003461.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66

Genes affected

ZYX (HGNC:13200): (zyxin) Focal adhesions are actin-rich structures that enable cells to adhere to the extracellular matrix and at which protein complexes involved in signal transduction assemble. Zyxin is a zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half. The proline-rich domain may interact with SH3 domains of proteins involved in signal transduction pathways while the LIM domains are likely involved in protein-protein binding. Zyxin may function as a messenger in the signal transduction pathway that mediates adhesion-stimulated changes in gene expression and may modulate the cytoskeletal organization of actin bundles. Alternative splicing results in multiple transcript variants that encode the same isoform. [provided by RefSeq, Jul 2008]

ZYX (HGNC:):

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/exons	MANE	Protein	UniProt
ZYX	NM_003461.5	c.452T>C	p.Leu151Pro	missense_variant	4/10	ENST00000322764.10	NP_003452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10	c.452T>C	p.Leu151Pro	missense_variant	4/10	1	NM_003461.5	ENSP00000324422.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.452T>C (p.L151P) alteration is located in exon 4 (coding exon 3) of the ZYX gene. This alteration results from a T to C substitution at nucleotide position 452, causing the leucine (L) at amino acid position 151 to be replaced by a proline (P). 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	1.0
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.054	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.60
MutPred		0.27		Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);
MVP		0.83
MPC		0.17
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.86
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr7-143079729;