rs11552742

Variant names:

• chr7-143382315-C-T
• rs11552742
• NM_003461.5:c.276C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-143382315-C-T
• chr7-143382315-C-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.951
• 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-AS2 (HGNC:56141): (FAM131B antisense RNA 2)

FAM131B (HGNC:22202): (family with sequence similarity 131 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.276C>T	p.Ala92Ala	synonymous	Exon 3 of 10	NP_003452.1	Q15942-1
	ZYX	NM_001010972.2		c.276C>T	p.Ala92Ala	synonymous	Exon 3 of 10	NP_001010972.1	Q15942-1
	ZYX	NM_001362783.2		c.276C>T	p.Ala92Ala	synonymous	Exon 3 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.276C>T	p.Ala92Ala	synonymous	Exon 3 of 10	ENSP00000324422.5	Q15942-1
	ZYX	ENST00000943399.1		c.276C>T	p.Ala92Ala	synonymous	Exon 3 of 11	ENSP00000613458.1
	ZYX	ENST00000869086.1		c.276C>T	p.Ala92Ala	synonymous	Exon 3 of 10	ENSP00000539145.1

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 462 AN: 151974 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00330 AC: 816 AN: 247368 AF XY: 0.00353

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 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.: 28 Cov.: 32 AF XY: 0.00499 AC XY: 3616 AN XY: 725186

African (AFR) AF: 0.000449 AC: 15 AN: 33382

American (AMR) AF: 0.00108 AC: 48 AN: 44262

Ashkenazi Jewish (ASJ) AF: 0.000694 AC: 18 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00516 AC: 444 AN: 86020

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53098

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5752

European-Non Finnish (NFE) AF: 0.00560 AC: 6220 AN: 1110026

Other (OTH) AF: 0.00380 AC: 229 AN: 60196

GnomAD4 genome AF: 0.00304 AC: 462 AN: 152092 Hom.: 1 Cov.: 32 AF XY: 0.00288 AC XY: 214 AN XY: 74354

African (AFR) AF: 0.000891 AC: 37 AN: 41506

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4820

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00518 AC: 352 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00429 Hom.: 1

Bravo AF: 0.00308

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00374

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		-0.95
PromoterAI		-0.031	Neutral
Mutation Taster		=300/0	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: rs11552742; hg19: chr7-143079408;