7-143382400-C-T

Position:

• chr7-143382400-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003461.5(ZYX):​c.361C>T​(p.Pro121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: -1.86

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044768125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYX	NM_003461.5	c.361C>T	p.Pro121Ser	missense_variant	3/10	ENST00000322764.10	NP_003452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10	c.361C>T	p.Pro121Ser	missense_variant	3/10	1	NM_003461.5	ENSP00000324422.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Oct 02, 2023

The c.361C>T (p.P121S) alteration is located in exon 3 (coding exon 2) of the ZYX gene. This alteration results from a C to T substitution at nucleotide position 361, causing the proline (P) at amino acid position 121 to be replaced by a serine (S). 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	Benign	0.089
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.2
DANN	Benign	0.78
DEOGEN2	Benign	0.079	T;.;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.050	D;T;D;D
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.19
MutPred		0.36		Gain of phosphorylation at P121 (P = 5e-04);.;Gain of phosphorylation at P121 (P = 5e-04);.;
MVP		0.061
MPC		0.10
ClinPred		0.071	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0
Varity_R		0.030
gMVP		0.21

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: chr7-143079493;