chr16-67878223-G-T

Variant names:

• chr16-67878223-G-T
• rs750996360
• NM_014329.5:c.952G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014329.5(EDC4):​c.952G>T​(p.Asp318Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D318G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EDC4 NM_014329.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.96
• Publications: 0 publications found

Genes affected

EDC4 (HGNC:17157): (enhancer of mRNA decapping 4) Predicted to be involved in deadenylation-independent decapping of nuclear-transcribed mRNA. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014329.5. 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
	EDC4	NM_014329.5	MANE Select	c.952G>T	p.Asp318Tyr	missense	Exon 8 of 29	NP_055144.3
	EDC4	NM_001427345.1		c.952G>T	p.Asp318Tyr	missense	Exon 8 of 28	NP_001414274.1	A0A8B0RAT7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDC4	ENST00000358933.10	TSL:1 MANE Select	c.952G>T	p.Asp318Tyr	missense	Exon 8 of 29	ENSP00000351811.5	Q6P2E9-1
	EDC4	ENST00000573992.5	TSL:1	n.331G>T		non_coding_transcript_exon	Exon 3 of 24
	EDC4	ENST00000851723.1		c.952G>T	p.Asp318Tyr	missense	Exon 8 of 29	ENSP00000521782.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		10
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-8.1	D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.55		Loss of solvent accessibility (P = 0.0509)
MVP		0.83
MPC		2.1
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.98

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: rs750996360; hg19: chr16-67912126;