dbSNP rs745510004: ZYX:p.Ala92Asp (chr7-143382314-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003461.5(ZYX):c.275C>A(p.Ala92Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

ZYX
NM_003461.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Variant links:

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 links:

FAM131B (HGNC:22202): (family with sequence similarity 131 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM131B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1983152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZYX	NM_003461.5 link	c.275C>A	p.Ala92Asp	missense_variant	Exon 3 of 10	ENST00000322764.10	NP_003452.1	Q15942-1Q96AF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10 link	c.275C>A	p.Ala92Asp	missense_variant	Exon 3 of 10	1	NM_003461.5	ENSP00000324422.5		Q15942-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247332

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;.;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.71

M_CAP

Benign

0.029

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.8

L;.;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.69

N;D;N;N

REVEL

Benign

0.12

Sift

Benign

0.085

T;D;T;T

Sift4G

Benign

0.17

T;D;D;T

Polyphen

0.92

P;.;.;.

Vest4

0.42

MutPred

0.26

Gain of relative solvent accessibility (P = 0.005);.;Gain of relative solvent accessibility (P = 0.005);.;

MVP

0.77

MPC

0.16

ClinPred

0.18

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.25

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over