rs571303442

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_024824.5(ZC3H14):c.2204+17_2204+41delGTTTTTCTCATGTCAGTTCAAATTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,612,820 control chromosomes in the GnomAD database, including 162 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.011 ( 14 hom., cov: 31)

Exomes 𝑓: 0.013 ( 148 hom. )

Consequence

ZC3H14
NM_024824.5 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:4

Conservation

PhyloP100: 1.09

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
intellectual disability, autosomal recessive 56
Inheritance: AR, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ZC3H14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 14-88610947-ATTCAAATTCGTTTTTCTCATGTCAG-A is Benign according to our data. Variant chr14-88610947-ATTCAAATTCGTTTTTCTCATGTCAG-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 254279.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5 link	c.2204+17_2204+41delGTTTTTCTCATGTCAGTTCAAATTC		intron_variant	Intron 16 of 16	ENST00000251038.10	NP_079100.2	Q6PJT7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10 link	c.2204+8_2204+32delTTCAAATTCGTTTTTCTCATGTCAG		splice_region_variant, intron_variant	Intron 16 of 16	1	NM_024824.5	ENSP00000251038.5		Q6PJT7-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1691

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00960

AC:

2413

AN:

251242

AF XY:

0.00978

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0281

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0130

AC:

19027

AN:

1460530

Hom.:

148

AF XY:

0.0128

AC XY:

9266

AN XY:

726658

show subpopulations

African (AFR)

AF:

0.0128

AC:

428

AN:

33444

American (AMR)

AF:

0.00447

AC:

200

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0287

AC:

750

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00590

AC:

509

AN:

86224

European-Finnish (FIN)

AF:

0.00382

AC:

204

AN:

53414

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0145

AC:

16111

AN:

1110792

Other (OTH)

AF:

0.0122

AC:

735

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

804

1607

2411

3214

4018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0111

AC:

1693

AN:

152290

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0127

AC:

528

AN:

41554

American (AMR)

AF:

0.00503

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00310

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

862

AN:

68016

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

166

250

333

416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0119

Hom.:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Intellectual disability, autosomal recessive 56

Pathogenic:1Uncertain:1Benign:1

Aug 22, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:curation

NG_050601.1(NM_024824.4):c.2204+17_2204+41del in ZC3H14 gene has an allele frequency of 0.028 in Ashkenazi Jewish subpopulation in the gnomAD database, including 22 homozygous occurrences. Benign computational verdict because benign prediction from GERP. Pak et al. reported three intellectual disability patients in a consanguineous family with the homozygous of this deletion. Haplotype of the single linkage interval with maximum LOD score of 2.5 in Family-2 (PMID: 21734151). Taken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2, BP4, PM3_Supporting, PP1_Strong. -

Dec 02, 2021

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:3

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZC3H14: BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 20, 2019

Knight Diagnostic Laboratories, Oregon Health and Sciences University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over