7-143382829-T-G

Position:

chr7-143382829-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000322764.10(ZYX):c.530T>G(p.Val177Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000728 in 1,607,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ZYX
ENST00000322764.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.463

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:

MIR6892 (HGNC:50053): (microRNA 6892) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6892 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019886732).

BS2

High AC in GnomAd4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYX	NM_003461.5 linkuse as main transcript	c.530T>G	p.Val177Gly	missense_variant	5/10	ENST00000322764.10	NP_003452.1
MIR6892	NR_106952.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10 linkuse as main transcript	c.530T>G	p.Val177Gly	missense_variant	5/10	1	NM_003461.5	ENSP00000324422	P2	Q15942-1
MIR6892	ENST00000612346.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000735

AC:

AN:

244738

Hom.:

AF XY:

0.0000908

AC XY:

AN XY:

132088

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000680

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000454

AC:

AN:

1455032

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

723302

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000469

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000336

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000799

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.530T>G (p.V177G) alteration is located in exon 5 (coding exon 4) of the ZYX gene. This alteration results from a T to G substitution at nucleotide position 530, causing the valine (V) at amino acid position 177 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

T;.;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.040

M_CAP

Benign

0.031

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.6

M;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;D;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.024

D;T;D;D

Polyphen

0.69

P;.;.;.

Vest4

0.25

MVP

0.42

MPC

0.28

ClinPred

0.11

GERP RS

1.1

Varity_R

0.35

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over