rs144601125

chr14-88572890-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_024824.5(ZC3H14):c.744T>C(p.Asp248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,614,192 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (9 hom.)
• Consequence: ZC3H14 NM_024824.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0450

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-88572890-T-C is Benign according to our data. Variant chr14-88572890-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 437308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-88572890-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.045 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H14	NM_024824.5	c.744T>C	p.Asp248=	synonymous_variant	6/17	ENST00000251038.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H14	ENST00000251038.10	c.744T>C	p.Asp248=	synonymous_variant	6/17	1	NM_024824.5	P3

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00145 AC: 365 AN: 251402 Hom.: 1 AF XY: 0.00149 AC XY: 203 AN XY: 135870

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.000555

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00241 AC: 3518 AN: 1461884 Hom.: 9 Cov.: 31 AF XY: 0.00234 AC XY: 1703 AN XY: 727242

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.000562

Gnomad4 NFE exome AF: 0.00301

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74482

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00232

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00224 Hom.: 1

Bravo AF: 0.00122

EpiCase AF: 0.00234

EpiControl AF: 0.00196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ZC3H14: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.1
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs144601125; hg19: chr14-89039234;