chr10-73139428-T-G

Position:

• chr10-73139428-T-G

Variant summary

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

The NM_007265.3(ECD):​c.1302A>C​(p.Lys434Asn) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ECD NM_007265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

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=0.088026226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ECD	NM_007265.3	c.1302A>C	p.Lys434Asn	missense_variant	11/14	ENST00000372979.9
ECD	NM_001135752.1	c.1401A>C	p.Lys467Asn	missense_variant	12/15
ECD	NM_001135753.1	c.1173A>C	p.Lys391Asn	missense_variant	10/13
ECD	NR_024203.1	n.1134A>C		non_coding_transcript_exon_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ECD	ENST00000372979.9	c.1302A>C	p.Lys434Asn	missense_variant	11/14	1	NM_007265.3	P1
ECD	ENST00000430082.6	c.1401A>C	p.Lys467Asn	missense_variant	12/15	1
ECD	ENST00000454759.6	c.1173A>C	p.Lys391Asn	missense_variant	10/13	1
ECD	ENST00000484976.6	c.*395A>C		3_prime_UTR_variant, NMD_transcript_variant	9/12	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

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 26, 2023

The c.1401A>C (p.K467N) alteration is located in exon 12 (coding exon 11) of the ECD gene. This alteration results from a A to C substitution at nucleotide position 1401, causing the lysine (K) at amino acid position 467 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.099	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.042	B;.;.
Vest4		0.058
MutPred		0.39		Loss of ubiquitination at K434 (P = 3e-04);.;.;
MVP		0.39
MPC		0.098
ClinPred		0.079	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs1007524995; hg19: chr10-74899186;