Genetic Variant ZC3HAV1:c.-72T>A (chr7-139109403-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020119.4(ZC3HAV1):c.-72T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,456,454 control chromosomes in the GnomAD database, including 16,627 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2510 hom., cov: 32)

Exomes 𝑓: 0.12 ( 14117 hom. )

Consequence

ZC3HAV1
NM_020119.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

12 publications found

Variant links:

Genes affected

ZC3HAV1 (HGNC:23721): (zinc finger CCCH-type containing, antiviral 1) This gene encodes a CCCH-type zinc finger protein. This antiviral protein inhibits viral replication by recruiting cellular RNA degradation machineries to degrade viral mRNAs. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses, including Ebola virus, HIV and SARS-CoV-2 (which causes COVID-19). [provided by RefSeq, Sep 2021]

ZC3HAV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4 link	c.-72T>A	5_prime_UTR_variant	Exon 1 of 13	ENST00000242351.10	NP_064504.2	Q7Z2W4-1
ZC3HAV1	NM_001363491.2 link	c.-72T>A	5_prime_UTR_variant	Exon 1 of 13		NP_001350420.1
ZC3HAV1	NM_024625.4 link	c.-72T>A	5_prime_UTR_variant	Exon 1 of 9		NP_078901.3	Q7Z2W4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZC3HAV1	ENST00000242351.10 link	c.-72T>A	5_prime_UTR_variant	Exon 1 of 13	1	NM_020119.4	ENSP00000242351.5	Q7Z2W4-1
ZC3HAV1	ENST00000471652.1 link	c.-72T>A	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000419855.1	Q7Z2W4-2
ZC3HAV1	ENST00000680309.1 link	c.-127-19644T>A	intron_variant	Intron 1 of 12			ENSP00000505045.1	A0A7P0T8C6
ZC3HAV1	ENST00000464606.5 link	c.-72T>A	upstream_gene_variant		5		ENSP00000418385.1	C9J6P4

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24775

AN:

151970

Hom.:

2511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.125

AC:

162872

AN:

1304366

Hom.:

14117

Cov.:

AF XY:

0.128

AC XY:

80996

AN XY:

634668

show subpopulations

African (AFR)

AF:

0.240

AC:

7027

AN:

29320

American (AMR)

AF:

0.108

AC:

2702

AN:

25074

Ashkenazi Jewish (ASJ)

AF:

0.0766

AC:

1523

AN:

19870

East Asian (EAS)

AF:

0.485

AC:

17026

AN:

35110

South Asian (SAS)

AF:

0.246

AC:

16368

AN:

66480

European-Finnish (FIN)

AF:

0.173

AC:

5736

AN:

33062

Middle Eastern (MID)

AF:

0.105

AC:

387

AN:

3676

European-Non Finnish (NFE)

AF:

0.101

AC:

104528

AN:

1037526

Other (OTH)

AF:

0.140

AC:

7575

AN:

54248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

7337

14674

22010

29347

36684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4242

8484

12726

16968

21210

<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:

0.163

AC:

24807

AN:

152088

Hom.:

2510

Cov.:

AF XY:

0.168

AC XY:

12521

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.240

AC:

9980

AN:

41500

American (AMR)

AF:

0.118

AC:

1807

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3470

East Asian (EAS)

AF:

0.437

AC:

2249

AN:

5150

South Asian (SAS)

AF:

0.269

AC:

1297

AN:

4826

European-Finnish (FIN)

AF:

0.169

AC:

1791

AN:

10594

Middle Eastern (MID)

AF:

0.106

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.103

AC:

6976

AN:

67944

Other (OTH)

AF:

0.144

AC:

304

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1031

2062

3093

4124

5155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.0417

Hom.:

Bravo

AF:

0.159

Asia WGS

AF:

0.334

AC:

1158

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.2

(source)

DANN

Benign

0.89

PhyloP100

-2.0

PromoterAI

0.091

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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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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