14-88575836-T-G

Variant names:

• chr14-88575836-T-G
• rs1469602
• NM_024824.5:c.1023-4T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024824.5(ZC3H14):​c.1023-4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,609,752 control chromosomes in the GnomAD database, including 392,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (28777 hom., cov: 32)
  • Exomes 𝑓: 0.70 (363285 hom.)
• Consequence: ZC3H14 NM_024824.5 splice_region, intron
• Scores: Splicing: ADA: 0.005529
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.04

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 14-88575836-T-G is Benign according to our data. Variant chr14-88575836-T-G is described in ClinVar as [Benign]. Clinvar id is 130765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5	c.1023-4T>G		splice_region_variant, intron_variant	Intron 7 of 16	ENST00000251038.10	NP_079100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10	c.1023-4T>G		splice_region_variant, intron_variant	Intron 7 of 16	1	NM_024824.5	ENSP00000251038.5

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89159 AN: 151866 Hom.: 28767 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.613

GnomAD2 exomes AF: 0.616 AC: 154469 AN: 250890 AF XY: 0.628

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.667

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.783

Gnomad NFE exome AF: 0.733

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.697 AC: 1015962 AN: 1457768 Hom.: 363285 Cov.: 32 AF XY: 0.696 AC XY: 504765 AN XY: 725516

Gnomad4 AFR exome AF: 0.315 AC: 10512 AN: 33366

Gnomad4 AMR exome AF: 0.440 AC: 19672 AN: 44706

Gnomad4 ASJ exome AF: 0.672 AC: 17550 AN: 26104

Gnomad4 EAS exome AF: 0.352 AC: 13937 AN: 39620

Gnomad4 SAS exome AF: 0.576 AC: 49645 AN: 86174

Gnomad4 FIN exome AF: 0.779 AC: 41376 AN: 53096

Gnomad4 NFE exome AF: 0.740 AC: 820031 AN: 1108748

Gnomad4 Remaining exome AF: 0.660 AC: 39757 AN: 60234

GnomAD4 genome AF: 0.587 AC: 89196 AN: 151984 Hom.: 28777 Cov.: 32 AF XY: 0.587 AC XY: 43650 AN XY: 74314

Gnomad4 AFR AF: 0.328 AC: 0.328306 AN: 0.328306

Gnomad4 AMR AF: 0.530 AC: 0.530492 AN: 0.530492

Gnomad4 ASJ AF: 0.668 AC: 0.667627 AN: 0.667627

Gnomad4 EAS AF: 0.377 AC: 0.376938 AN: 0.376938

Gnomad4 SAS AF: 0.595 AC: 0.594831 AN: 0.594831

Gnomad4 FIN AF: 0.791 AC: 0.790997 AN: 0.790997

Gnomad4 NFE AF: 0.735 AC: 0.735356 AN: 0.735356

Gnomad4 OTH AF: 0.613 AC: 0.612903 AN: 0.612903

Alfa AF: 0.678 Hom.: 147275

Bravo AF: 0.552

Asia WGS AF: 0.463 AC: 1611 AN: 3478

EpiCase AF: 0.717

EpiControl AF: 0.717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0055
dbscSNV1_RF	Benign	0.15
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: rs1469602; hg19: chr14-89042180; COSMIC: COSV51769735; COSMIC: COSV51769735;