6-158785410-G-C

Variant names:

• chr6-158785410-G-C
• rs35947532
• NM_001111077.2:c.366C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001111077.2(EZR):​c.366C>G​(p.Ala122Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A122A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EZR NM_001111077.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.96
• Publications: 4 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-158785410-G-C is Benign according to our data. Variant chr6-158785410-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.96 with no splicing effect.

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.366C>G	p.Ala122Ala	synonymous	Exon 5 of 14	NP_001104547.1	P15311
	EZR	NM_003379.5		c.366C>G	p.Ala122Ala	synonymous	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.366C>G	p.Ala122Ala	synonymous	Exon 5 of 14	ENSP00000356042.3	P15311
	EZR	ENST00000337147.11	TSL:1	c.366C>G	p.Ala122Ala	synonymous	Exon 4 of 13	ENSP00000338934.7	P15311
	EZR	ENST00000852607.1		c.504C>G	p.Ala168Ala	synonymous	Exon 6 of 15	ENSP00000522666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.98
DANN	Benign	0.53
PhyloP100		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35947532; hg19: chr6-159206442;