Variant 7-143382315-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003461.5(ZYX):c.276C>T(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,610,402 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 28 hom. )

Consequence

ZYX
NM_003461.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.951

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:

ZYX (HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-143382315-C-T is Benign according to our data. Variant chr7-143382315-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658117.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.951 with no splicing effect.

BS2

High AC in GnomAd4 at 462 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYX	NM_003461.5 linkuse as main transcript	c.276C>T	p.Ala92Ala	synonymous_variant	3/10	ENST00000322764.10	NP_003452.1	Q15942-1Q96AF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10 linkuse as main transcript	c.276C>T	p.Ala92Ala	synonymous_variant	3/10	1	NM_003461.5	ENSP00000324422.5		Q15942-1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00518

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00330

AC:

816

AN:

247368

Hom.:

AF XY:

0.00353

AC XY:

474

AN XY:

134096

show subpopulations

Gnomad AFR exome

AF:

0.000688

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.000513

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00514

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

AF:

0.00484

AC:

7060

AN:

1458310

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

3616

AN XY:

725186

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.000694

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00516

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00560

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00304

AC:

462

AN:

152092

Hom.:

Cov.:

AF XY:

0.00288

AC XY:

214

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00518

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00429

Hom.:

Bravo

AF:

0.00308

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00374

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ZYX: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.94

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

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