10-73139347-T-C

Position:

• chr10-73139347-T-C

Variant summary

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

The NM_007265.3(ECD):​c.1383A>G​(p.Ile461Met) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417

Genes affected

ECD (HGNC:17029): (ecdysoneless cell cycle regulator) Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol 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=0.16720816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECD	NM_007265.3	c.1383A>G	p.Ile461Met	missense_variant	11/14	ENST00000372979.9
ECD	NM_001135752.1	c.1482A>G	p.Ile494Met	missense_variant	12/15
ECD	NM_001135753.1	c.1254A>G	p.Ile418Met	missense_variant	10/13
ECD	NR_024203.1	n.1215A>G		non_coding_transcript_exon_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECD	ENST00000372979.9	c.1383A>G	p.Ile461Met	missense_variant	11/14	1	NM_007265.3	P1
ECD	ENST00000430082.6	c.1482A>G	p.Ile494Met	missense_variant	12/15	1
ECD	ENST00000454759.6	c.1254A>G	p.Ile418Met	missense_variant	10/13	1
ECD	ENST00000484976.6	c.*476A>G		3_prime_UTR_variant, NMD_transcript_variant	9/12	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.1482A>G (p.I494M) alteration is located in exon 12 (coding exon 11) of the ECD gene. This alteration results from a A to G substitution at nucleotide position 1482, causing the isoleucine (I) at amino acid position 494 to be replaced by a methionine (M). 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	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.059	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.16	B;.;.
Vest4		0.36
MutPred		0.50		Gain of ubiquitination at K463 (P = 0.0768);.;.;
MVP		0.18
MPC		0.22
ClinPred		0.37	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.076
gMVP		0.26

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: chr10-74899105;