NM_003797.5:c.78C>G

Variant names:

• chr11-86245307-C-G
• NM_003797.5:c.78C>G

Variant summary

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

The NM_003797.5(EED):​c.78C>G​(p.Asp26Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D26D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EED NM_003797.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

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=0.1172868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EED	NM_003797.5	c.78C>G	p.Asp26Glu	missense_variant	Exon 1 of 12	ENST00000263360.11	NP_003788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EED	ENST00000263360.11	c.78C>G	p.Asp26Glu	missense_variant	Exon 1 of 12	1	NM_003797.5	ENSP00000263360.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461314 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726920

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.33
MutPred		0.23		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.46
MPC		0.0015
ClinPred		0.16	T
GERP RS		0.73
Varity_R		0.16
gMVP		0.30

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: chr11-85956349; COSMIC: COSV54556391;