Genetic Variant ZC3H14:c.*9200delA (chr14-88620934-TA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024824.5(ZC3H14):c.*9200delA 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 0.0056 ( 3 hom., cov: 0)

Exomes 𝑓: 0.16 ( 1 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H14	NM_024824.5 link	c.*9200delA		3_prime_UTR_variant	Exon 17 of 17	ENST00000251038.10	NP_079100.2	Q6PJT7-1
EML5	NM_183387.3 link	c.5203-9delT		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.*9200delA		3_prime_UTR_variant	Exon 17 of 17	1	NM_024824.5	ENSP00000251038.5		Q6PJT7-1
EML5	ENST00000554922.6 link	c.5203-9delT		intron_variant	Intron 38 of 43	5	NM_183387.3	ENSP00000451998.1		Q05BV3-5

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

771

AN:

138808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00391

Gnomad ASJ

AF:

0.00119

Gnomad EAS

AF:

0.00396

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.0122

Gnomad MID

AF:

0.00352

Gnomad NFE

AF:

0.00262

Gnomad OTH

AF:

0.00535

GnomAD2 exomes

AF:

0.250

AC:

13084

AN:

52316

AF XY:

0.251

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.164

AC:

188385

AN:

1148772

Hom.:

Cov.:

AF XY:

0.166

AC XY:

93181

AN XY:

560256

show subpopulations

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

African (AFR)

AF:

0.212

AC:

5292

AN:

24910

American (AMR)

AF:

0.186

AC:

2949

AN:

15828

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

2853

AN:

17216

East Asian (EAS)

AF:

0.226

AC:

6882

AN:

30408

South Asian (SAS)

AF:

0.217

AC:

12009

AN:

55246

European-Finnish (FIN)

AF:

0.178

AC:

6041

AN:

33950

Middle Eastern (MID)

AF:

0.134

AC:

621

AN:

4638

European-Non Finnish (NFE)

AF:

0.156

AC:

143398

AN:

919222

Other (OTH)

AF:

0.176

AC:

8340

AN:

47354

⚠️ 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: 0.285

Heterozygous variant carriers

14909

29818

44728

59637

74546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5358

10716

16074

21432

26790

<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:

0.00560

AC:

777

AN:

138816

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

407

AN XY:

66668

show subpopulations

African (AFR)

AF:

0.0113

AC:

423

AN:

37396

American (AMR)

AF:

0.00390

AC:

AN:

13832

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

3366

East Asian (EAS)

AF:

0.00398

AC:

AN:

4778

South Asian (SAS)

AF:

0.00140

AC:

AN:

4272

European-Finnish (FIN)

AF:

0.0122

AC:

AN:

7358

Middle Eastern (MID)

AF:

0.00373

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00262

AC:

170

AN:

64784

Other (OTH)

AF:

0.00534

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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14-88620934-TAAAAAA-TAAAAA

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