rs780416130

Variant names:

• chr7-143381728-C-A
• rs780416130
• NM_003461.5:c.157C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-143381728-C-A
• chr7-143381728-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_003461.5(ZYX):​c.157C>A​(p.Gln53Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000352 in 1,447,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: ZYX NM_003461.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

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

FAM131B-AS2 (HGNC:56141): (FAM131B antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21386173).
• BS2: High AC in GnomAdExome4 at 51 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003461.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYX	NM_003461.5	MANE Select	c.157C>A	p.Gln53Lys	missense	Exon 2 of 10	NP_003452.1	Q15942-1
	ZYX	NM_001010972.2		c.157C>A	p.Gln53Lys	missense	Exon 2 of 10	NP_001010972.1	Q15942-1
	ZYX	NM_001362783.2		c.157C>A	p.Gln53Lys	missense	Exon 2 of 9	NP_001349712.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZYX	ENST00000322764.10	TSL:1 MANE Select	c.157C>A	p.Gln53Lys	missense	Exon 2 of 10	ENSP00000324422.5	Q15942-1
	ZYX	ENST00000943399.1		c.157C>A	p.Gln53Lys	missense	Exon 2 of 11	ENSP00000613458.1
	ZYX	ENST00000869086.1		c.157C>A	p.Gln53Lys	missense	Exon 2 of 10	ENSP00000539145.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000187 AC: 4 AN: 213398 AF XY: 0.0000169

Gnomad AFR exome AF: 0.0000913

Gnomad AMR exome AF: 0.0000307

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000217

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000352 AC: 51 AN: 1447228 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 29 AN XY: 719076

African (AFR) AF: 0.0000305 AC: 1 AN: 32840

American (AMR) AF: 0.0000228 AC: 1 AN: 43772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25800

East Asian (EAS) AF: 0.00 AC: 0 AN: 38506

South Asian (SAS) AF: 0.00 AC: 0 AN: 84528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000434 AC: 48 AN: 1105774

Other (OTH) AF: 0.0000168 AC: 1 AN: 59656

GnomAD4 genome Cov.: 33

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000170 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.89
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.72	D
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.78	T
Polyphen		0.98	D
Vest4		0.39
MutPred		0.27		Gain of ubiquitination at Q53 (P = 0.0042)
MVP		0.56
MPC		0.13
ClinPred		0.11	T
GERP RS		3.1
PromoterAI		-0.098	Neutral
Varity_R		0.33
gMVP		0.27
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs780416130; hg19: chr7-143078821;