rs369362135

Variant names:

• chr16-67873338-C-A
• NM_014329.5:c.77C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-67873338-C-A
• chr16-67873338-C-G
• chr16-67873338-C-T

Variant summary

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

The NM_014329.5(EDC4):​c.77C>A​(p.Ala26Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000154 in 1,302,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. A26G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EDC4 NM_014329.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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

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=0.09990424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDC4	NM_014329.5	c.77C>A	p.Ala26Glu	missense_variant	Exon 1 of 29	ENST00000358933.10	NP_055144.3
EDC4	NM_001427345.1	c.77C>A	p.Ala26Glu	missense_variant	Exon 1 of 28		NP_001414274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDC4	ENST00000358933.10	c.77C>A	p.Ala26Glu	missense_variant	Exon 1 of 29	1	NM_014329.5	ENSP00000351811.5
EDC4	ENST00000572221.5	n.287C>A		non_coding_transcript_exon_variant	Exon 1 of 28	2
EDC4	ENST00000536072.6	n.-34C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1302096 Hom.: 0 Cov.: 30 AF XY: 0.00000156 AC XY: 1 AN XY: 641058

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: 0.00000192

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.056
Sift	Benign	0.23	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.40		Loss of sheet (P = 0.0025);
MVP		0.22
MPC		0.92
ClinPred		0.74	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.19

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: chr16-67907241;