rs45518831

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.64

Publications

11 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 212620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024824.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3H14	NM_024824.5	MANE Select	c.1304C>T	p.Ser435Phe	missense	Exon 10 of 17	NP_079100.2
ZC3H14	NM_001160103.2		c.1304C>T	p.Ser435Phe	missense	Exon 10 of 17	NP_001153575.1	Q6PJT7-2
ZC3H14	NM_001326310.2		c.1304C>T	p.Ser435Phe	missense	Exon 10 of 17	NP_001313239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZC3H14	ENST00000251038.10	TSL:1 MANE Select	c.1304C>T	p.Ser435Phe	missense	Exon 10 of 17	ENSP00000251038.5	Q6PJT7-1
ZC3H14	ENST00000556000.5	TSL:1	c.1049C>T	p.Ser350Phe	missense	Exon 6 of 13	ENSP00000451054.1	H0YJA2
ZC3H14	ENST00000336693.8	TSL:1	c.1202C>T	p.Ser401Phe	missense	Exon 10 of 15	ENSP00000338002.4	Q6PJT7-4

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

555

AN:

152130

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00411

AC:

1033

AN:

251318

AF XY:

0.00417

show subpopulations

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 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.:

Cov.:

AF XY:

0.00325

AC XY:

2362

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33478

American (AMR)

AF:

0.000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.00158

AC:

136

AN:

86252

European-Finnish (FIN)

AF:

0.0172

AC:

921

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00307

AC:

3412

AN:

1111920

Other (OTH)

AF:

0.00310

AC:

187

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

238

476

714

952

1190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.00365

AC:

556

AN:

152248

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

319

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41566

American (AMR)

AF:

0.00183

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00125

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00444

AC:

302

AN:

68004

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00383

Hom.:

Bravo

AF:

0.00203

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00439

AC:

533

EpiCase

AF:

0.00322

EpiControl

AF:

0.00279

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.30

MutationAssessor

Benign

2.0

PhyloP100

1.6

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.50

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.61

MVP

0.093

MPC

1.5

ClinPred

0.020

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.64

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over