11-86245241-G-T

Position:

• chr11-86245241-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003797.5(EED):​c.12G>T​(p.Arg4Ser) variant causes a missense 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: EED NM_003797.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64

Genes affected

EED (HGNC:3188): (embryonic ectoderm development) 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 interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21074116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EED	NM_003797.5	c.12G>T	p.Arg4Ser	missense_variant	1/12	ENST00000263360.11	NP_003788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EED	ENST00000263360.11	c.12G>T	p.Arg4Ser	missense_variant	1/12	1	NM_003797.5	ENSP00000263360	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.12G>T (p.R4S) alteration is located in exon 1 (coding exon 1) of the EED gene. This alteration results from a G to T substitution at nucleotide position 12, causing the arginine (R) at amino acid position 4 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T;T;.;.
Eigen	Benign	0.079
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.0	N;.;N;N
MutationTaster	Benign	0.70	N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.17	N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.034	D;D;D;D
Sift4G	Benign	0.97	T;T;T;T
Polyphen		0.46	P;P;B;B
Vest4		0.089
MutPred		0.26		Gain of glycosylation at R4 (P = 0.0175);Gain of glycosylation at R4 (P = 0.0175);Gain of glycosylation at R4 (P = 0.0175);Gain of glycosylation at R4 (P = 0.0175);
MVP		0.79
MPC		0.0012
ClinPred		0.51	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-85956283;