Genetic Variant ZC3H14:c.*9199_*9200dupAA (chr14-88620934-T-TAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_024824.5(ZC3H14):c.*9199_*9200dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 22 hom., cov: 0)

Exomes 𝑓: 0.0056 ( 0 hom. )

Consequence

ZC3H14
NM_024824.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.252

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 links:

EML5 (HGNC:18197): (EMAP like 5) Predicted to enable microtubule binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

EML5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0132 (1835/138866) while in subpopulation AFR AF = 0.0351 (1311/37398). AF 95% confidence interval is 0.0335. There are 22 homozygotes in GnomAd4. There are 811 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5 link	c.9199_9200dupAA		3_prime_UTR_variant	Exon 17 of 17	ENST00000251038.10	NP_079100.2	Q6PJT7-1
EML5	NM_183387.3 link	c.5203-10_5203-9dupTT		intron_variant	Intron 38 of 43	ENST00000554922.6	NP_899243.1	Q05BV3-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H14	ENST00000251038.10 link	c.9199_9200dupAA		3_prime_UTR_variant	Exon 17 of 17	1	NM_024824.5	ENSP00000251038.5		Q6PJT7-1
EML5	ENST00000554922.6 link	c.5203-10_5203-9dupTT		intron_variant	Intron 38 of 43	5	NM_183387.3	ENSP00000451998.1		Q05BV3-5

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

1833

AN:

138858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00450

Gnomad AMR

AF:

0.00905

Gnomad ASJ

AF:

0.0146

Gnomad EAS

AF:

0.00167

Gnomad SAS

AF:

0.00233

Gnomad FIN

AF:

0.00285

Gnomad MID

AF:

0.00704

Gnomad NFE

AF:

0.00441

Gnomad OTH

AF:

0.0102

GnomAD2 exomes

AF:

0.0114

AC:

597

AN:

52316

AF XY:

0.0113

show subpopulations

Gnomad AFR exome

AF:

0.0241

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.00680

Gnomad EAS exome

AF:

0.00840

Gnomad FIN exome

AF:

0.00996

Gnomad NFE exome

AF:

0.0102

Gnomad OTH exome

AF:

0.0169

GnomAD4 exome

AF:

0.00557

AC:

6853

AN:

1229610

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

3315

AN XY:

599252

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0195

AC:

519

AN:

26596

American (AMR)

AF:

0.00903

AC:

152

AN:

16824

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

200

AN:

18520

East Asian (EAS)

AF:

0.00297

AC:

AN:

33030

South Asian (SAS)

AF:

0.00692

AC:

400

AN:

57766

European-Finnish (FIN)

AF:

0.00473

AC:

173

AN:

36562

Middle Eastern (MID)

AF:

0.00635

AC:

AN:

4880

European-Non Finnish (NFE)

AF:

0.00503

AC:

4952

AN:

984468

Other (OTH)

AF:

0.00644

AC:

328

AN:

50964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.289

Heterozygous variant carriers

514

1028

1542

2056

2570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

214

428

642

856

1070

<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:

0.0132

AC:

1835

AN:

138866

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

811

AN XY:

66706

show subpopulations

African (AFR)

AF:

0.0351

AC:

1311

AN:

37398

American (AMR)

AF:

0.00903

AC:

125

AN:

13836

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

AN:

3366

East Asian (EAS)

AF:

0.00167

AC:

AN:

4780

South Asian (SAS)

AF:

0.00234

AC:

AN:

4272

European-Finnish (FIN)

AF:

0.00285

AC:

AN:

7380

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00441

AC:

286

AN:

64804

Other (OTH)

AF:

0.0101

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

164

246

328

410

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.25

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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14-88620934-TAAAAAA-TAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over