14-75071724-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024643.4(ZC2HC1C):c.1151A>T(p.Glu384Val) 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. 13/21 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: ZC2HC1C NM_024643.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

Genes affected

ZC2HC1C (HGNC:20354): (zinc finger C2HC-type containing 1C) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.273329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC2HC1C	NM_024643.4	c.1151A>T	p.Glu384Val	missense_variant	2/3	ENST00000524913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC2HC1C	ENST00000524913.3	c.1151A>T	p.Glu384Val	missense_variant	2/3	2	NM_024643.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Aug 23, 2021

The c.1151A>T (p.E384V) alteration is located in exon 2 (coding exon 1) of the ZC2HC1C gene. This alteration results from a A to T substitution at nucleotide position 1151, causing the glutamic acid (E) at amino acid position 384 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.81	D;D;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.34
MutPred		0.15		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.43
MPC		0.55
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.27

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: chr14-75538427;