rs764670721

Positions:

• chr14-88568130-C-A
• chr14-88568130-C-G

Variant summary

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

The NM_024824.5(ZC3H14):​c.171C>A​(p.Asn57Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H14 NM_024824.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86

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]

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=0.36571294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H14	NM_024824.5	c.171C>A	p.Asn57Lys	missense_variant	3/17	ENST00000251038.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H14	ENST00000251038.10	c.171C>A	p.Asn57Lys	missense_variant	3/17	1	NM_024824.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;T;.;T;T;.;.;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.79	N;N;.;.;.;.;N;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D;N;D;N;D;D;D;D;D;N;D
REVEL	Uncertain	0.31
Sift	Benign	0.072	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Uncertain	0.028	D;D;T;D;T;T;D;D;D;D;D
Polyphen		0.98	D;P;.;.;.;.;.;.;.;.;.
Vest4		0.45
MutPred		0.46		Gain of methylation at N57 (P = 0.0283);Gain of methylation at N57 (P = 0.0283);.;Gain of methylation at N57 (P = 0.0283);.;.;Gain of methylation at N57 (P = 0.0283);Gain of methylation at N57 (P = 0.0283);.;.;.;
MVP		0.093
MPC		2.4
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.36

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: rs764670721; hg19: chr14-89034474;