7-143381722-G-C

Variant names:

• chr7-143381722-G-C
• rs779242588
• NM_003461.5:c.151G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003461.5(ZYX):​c.151G>C​(p.Gly51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,480 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G51E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZYX NM_003461.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.151G>C	p.Gly51Arg	missense	Exon 2 of 10	NP_003452.1	Q15942-1
	ZYX	NM_001010972.2		c.151G>C	p.Gly51Arg	missense	Exon 2 of 10	NP_001010972.1	Q15942-1
	ZYX	NM_001362783.2		c.151G>C	p.Gly51Arg	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.151G>C	p.Gly51Arg	missense	Exon 2 of 10	ENSP00000324422.5	Q15942-1
	ZYX	ENST00000943399.1		c.151G>C	p.Gly51Arg	missense	Exon 2 of 11	ENSP00000613458.1
	ZYX	ENST00000869086.1		c.151G>C	p.Gly51Arg	missense	Exon 2 of 10	ENSP00000539145.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000930 AC: 2 AN: 215028 AF XY: 0.0000168

Gnomad AFR exome AF: 0.00

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: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447480 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 719216

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.0000229 AC: 1 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 38626

South Asian (SAS) AF: 0.00 AC: 0 AN: 84570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105782

Other (OTH) AF: 0.00 AC: 0 AN: 59660

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.69	D
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.50
MutPred		0.31		Loss of loop (P = 0.0374)
MVP		0.75
MPC		0.12
ClinPred		0.69	D
GERP RS		3.9
PromoterAI		0.0023	Neutral
Varity_R		0.42
gMVP		0.26
Mutation Taster		=83/17	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: rs779242588; hg19: chr7-143078815;