NM_004456.5:c.118-6_118-4delTTT

Variant names:

• chr7-148846601-TAAA-T
• rs3214332
• NM_004456.5:c.118-6_118-4delTTT

Variant summary

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

The NM_004456.5(EZH2):​c.118-6_118-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EZH2 NM_004456.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• Publications: 0 publications found

Genes affected

EZH2 (HGNC:3527): (enhancer of zeste 2 polycomb repressive complex 2 subunit) This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

EZH2 Gene-Disease associations (from GenCC):

• Weaver syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004456.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EZH2	NM_004456.5	MANE Select	c.118-6_118-4delTTT		splice_region intron	N/A	NP_004447.2
	EZH2	NM_001203247.2		c.118-6_118-4delTTT		splice_region intron	N/A	NP_001190176.1
	EZH2	NM_001203248.2		c.118-6_118-4delTTT		splice_region intron	N/A	NP_001190177.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EZH2	ENST00000320356.7	TSL:1 MANE Select	c.118-6_118-4delTTT		splice_region intron	N/A	ENSP00000320147.2
	EZH2	ENST00000460911.5	TSL:1	c.118-6_118-4delTTT		splice_region intron	N/A	ENSP00000419711.1
	EZH2	ENST00000350995.6	TSL:1	c.118-6_118-4delTTT		splice_region intron	N/A	ENSP00000223193.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150380 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1314328 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 654460

African (AFR) AF: 0.00 AC: 0 AN: 28370

American (AMR) AF: 0.00 AC: 0 AN: 38448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23398

East Asian (EAS) AF: 0.00 AC: 0 AN: 36162

South Asian (SAS) AF: 0.00 AC: 0 AN: 76398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5322

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1003708

Other (OTH) AF: 0.00 AC: 0 AN: 54010

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150380 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73278

African (AFR) AF: 0.00 AC: 0 AN: 40992

American (AMR) AF: 0.00 AC: 0 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67552

Other (OTH) AF: 0.00 AC: 0 AN: 2072

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3214332; hg19: chr7-148543693;