rs45518831

chr14-88596758-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_024824.5(ZC3H14):c.1304C>T(p.Ser435Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,982 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (29 hom.)
• Consequence: ZC3H14 NM_024824.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.64

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072610974).
• BP6: Variant 14-88596758-C-T is Benign according to our data. Variant chr14-88596758-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 212620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-88596758-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H14	NM_024824.5	c.1304C>T	p.Ser435Phe	missense_variant	10/17	ENST00000251038.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H14	ENST00000251038.10	c.1304C>T	p.Ser435Phe	missense_variant	10/17	1	NM_024824.5	P3

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152130 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00411 AC: 1033 AN: 251318 Hom.: 6 AF XY: 0.00417 AC XY: 567 AN XY: 135832

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0171

Gnomad NFE exome AF: 0.00494

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00322 AC: 4704 AN: 1461734 Hom.: 29 Cov.: 31 AF XY: 0.00325 AC XY: 2362 AN XY: 727172

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000671

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00158

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.00307

Gnomad4 OTH exome AF: 0.00310

GnomAD4 genome AF: 0.00365 AC: 556 AN: 152248 Hom.: 3 Cov.: 33 AF XY: 0.00429 AC XY: 319 AN XY: 74432

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00377 Hom.: 4

Bravo AF: 0.00203

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00439 AC: 533

EpiCase AF: 0.00322

EpiControl AF: 0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ZC3H14: BP4, BS2 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.;.;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
MetaRNN	Benign	0.0073	T;T;T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	2.0	M;.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.0	D;N;D;N;N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;P;.
Vest4		0.61
MVP		0.093
MPC		1.5
ClinPred		0.020	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.64

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: rs45518831; hg19: chr14-89063102;