rs528409234

Variant names:

• chr6-158785391-C-T
• rs528409234
• NM_001111077.2:c.385G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-158785391-C-T
• chr6-158785391-C-A

Variant summary

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

The NM_001111077.2(EZR):​c.385G>A​(p.Ala129Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000204 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: EZR NM_001111077.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.98
• Publications: 3 publications found

Genes affected

EZR (HGNC:12691): (ezrin) The cytoplasmic peripheral membrane protein encoded by this gene functions as a protein-tyrosine kinase substrate in microvilli. As a member of the ERM protein family, this protein serves as an intermediate between the plasma membrane and the actin cytoskeleton. This protein plays a key role in cell surface structure adhesion, migration and organization, and it has been implicated in various human cancers. A pseudogene located on chromosome 3 has been identified for this gene. Alternatively spliced variants have also been described for this gene. [provided by RefSeq, Jul 2008]

EZR Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111077.2. 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
	EZR	NM_001111077.2	MANE Select	c.385G>A	p.Ala129Thr	missense	Exon 5 of 14	NP_001104547.1	P15311
	EZR	NM_003379.5		c.385G>A	p.Ala129Thr	missense	Exon 4 of 13	NP_003370.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EZR	ENST00000367075.4	TSL:1 MANE Select	c.385G>A	p.Ala129Thr	missense	Exon 5 of 14	ENSP00000356042.3	P15311
	EZR	ENST00000337147.11	TSL:1	c.385G>A	p.Ala129Thr	missense	Exon 4 of 13	ENSP00000338934.7	P15311
	EZR	ENST00000852607.1		c.523G>A	p.Ala175Thr	missense	Exon 6 of 15	ENSP00000522666.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000195 AC: 49 AN: 251486 AF XY: 0.000199

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000207 AC: 302 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.000204 AC XY: 148 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000236 AC: 262 AN: 1112012

Other (OTH) AF: 0.000281 AC: 17 AN: 60396

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74482

African (AFR) AF: 0.0000962 AC: 4 AN: 41584

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000173 Hom.: 0

Bravo AF: 0.000268

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000206 AC: 25

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.76
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.61		Loss of catalytic residue at A129 (P = 0.0519)
MVP		0.76
MPC		1.0
ClinPred		0.49	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.57
Mutation Taster		=24/76	disease causing

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: rs528409234; hg19: chr6-159206423;