chr14-88572693-G-A

Position:

• chr14-88572693-G-A

Variant summary

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

The NM_024824.5(ZC3H14):​c.547G>A​(p.Asp183Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZC3H14 NM_024824.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99

Genes affected

ZC3H14 (HGNC:20509): (zinc finger CCCH-type containing 14) The protein encoded by this gene is a poly(A)-binding protein that can affect gene expression and poly(A) tail length. The encoded protein may influence mRNA stability, nuclear export, and translation. [provided by RefSeq, May 2016]

ZC3H14 (HGNC:):

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=0.24666974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.547G>A	p.Asp183Asn	missense_variant	6/17	ENST00000251038.10	NP_079100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10	c.547G>A	p.Asp183Asn	missense_variant	6/17	1	NM_024824.5	ENSP00000251038.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 06, 2024

The c.547G>A (p.D183N) alteration is located in exon 6 (coding exon 6) of the ZC3H14 gene. This alteration results from a G to A substitution at nucleotide position 547, causing the aspartic acid (D) at amino acid position 183 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	0.33
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;.;.;T;.;T;.;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	L;L;.;.;.;.;L;L;.
MutationTaster	Benign	0.58	D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.96	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.055
Sift	Benign	0.21	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T;T
Polyphen		0.57	P;B;P;.;.;.;.;.;.
Vest4		0.52
MutPred		0.21		Loss of disorder (P = 0.3192);Loss of disorder (P = 0.3192);Loss of disorder (P = 0.3192);.;.;.;Loss of disorder (P = 0.3192);Loss of disorder (P = 0.3192);.;
MVP		0.043
MPC		0.41
ClinPred		0.79	D
GERP RS		5.8
Varity_R		0.026
gMVP		0.25

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: chr14-89039037;