Genetic Variant NM_020119.4:c.-72T>G (chr7-139109403-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020119.4(ZC3HAV1):c.-72T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ZC3HAV1
NM_020119.4 5_prime_UTR_premature_start_codon_gain

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZC3HAV1	NM_020119.4	MANE Select	c.-72T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_064504.2
ZC3HAV1	NM_020119.4	MANE Select	c.-72T>G	5_prime_UTR	Exon 1 of 13	NP_064504.2
ZC3HAV1	NM_001363491.2		c.-72T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001350420.1	C9J6P4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZC3HAV1	ENST00000242351.10	TSL:1 MANE Select	c.-72T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000242351.5	Q7Z2W4-1
ZC3HAV1	ENST00000471652.1	TSL:1	c.-72T>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000419855.1	Q7Z2W4-2
ZC3HAV1	ENST00000242351.10	TSL:1 MANE Select	c.-72T>G	5_prime_UTR	Exon 1 of 13	ENSP00000242351.5	Q7Z2W4-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1304618

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

634784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29322

American (AMR)

AF:

0.00

AC:

AN:

25080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19872

East Asian (EAS)

AF:

0.00

AC:

AN:

35120

South Asian (SAS)

AF:

0.00

AC:

AN:

66496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3676

European-Non Finnish (NFE)

AF:

9.64e-7

AC:

AN:

1037742

Other (OTH)

AF:

0.0000184

AC:

AN:

54248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-2.0

PromoterAI

-0.38

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over