7-143381759-T-G

Position:

• chr7-143381759-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000322764.10(ZYX):​c.188T>G​(p.Ile63Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00195 in 1,581,214 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (14 hom.)
• Consequence: ZYX ENST00000322764.10 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.50

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]

FAM131B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044882298).
• BP6: Variant 7-143381759-T-G is Benign according to our data. Variant chr7-143381759-T-G is described in ClinVar as [Benign]. Clinvar id is 784501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00741 (1127/152170) while in subpopulation AFR AF= 0.0224 (931/41558). AF 95% confidence interval is 0.0212. There are 13 homozygotes in gnomad4. There are 548 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1127 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYX	NM_003461.5	c.188T>G	p.Ile63Ser	missense_variant	2/10	ENST00000322764.10	NP_003452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYX	ENST00000322764.10	c.188T>G	p.Ile63Ser	missense_variant	2/10	1	NM_003461.5	ENSP00000324422	P2

Frequencies

GnomAD3 genomes AF: 0.00739 AC: 1124 AN: 152052 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00647

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.00240 AC: 457 AN: 190776 Hom.: 3 AF XY: 0.00194 AC XY: 206 AN XY: 106004

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00488

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000376

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000963

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00137 AC: 1955 AN: 1429044 Hom.: 14 Cov.: 31 AF XY: 0.00129 AC XY: 915 AN XY: 708076

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.00499

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.0000482

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000688

Gnomad4 OTH exome AF: 0.00330

GnomAD4 genome AF: 0.00741 AC: 1127 AN: 152170 Hom.: 13 Cov.: 33 AF XY: 0.00737 AC XY: 548 AN XY: 74406

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.00249 Hom.: 1

Bravo AF: 0.00846

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0144 AC: 51

ESP6500EA AF: 0.00107 AC: 8

ExAC AF: 0.00215 AC: 244

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	0.015
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.86	D
MetaRNN	Benign	0.0045	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	0.88	D;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N;D;N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.84	P;.;.
Vest4		0.36
MVP		0.75
MPC		0.15
ClinPred		0.024	T
GERP RS		4.0
Varity_R		0.30
gMVP		0.32

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

Other links and lift over

dbSNP: rs201850974; hg19: chr7-143078852;