Genetic Variant ZC3HAV1:p.Leu806Arg (chr7-139053483-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020119.4(ZC3HAV1):c.2417T>G(p.Leu806Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZC3HAV1
NM_020119.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.391

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4 link	c.2417T>G	p.Leu806Arg	missense_variant	Exon 12 of 13	ENST00000242351.10	NP_064504.2	Q7Z2W4-1
ZC3HAV1	NM_001363491.2 link	c.2783T>G	p.Leu928Arg	missense_variant	Exon 12 of 13		NP_001350420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZC3HAV1	ENST00000242351.10 link	c.2417T>G	p.Leu806Arg	missense_variant	Exon 12 of 13	1	NM_020119.4	ENSP00000242351.5	Q7Z2W4-1
ZC3HAV1	ENST00000464606.5 link	c.2783T>G	p.Leu928Arg	missense_variant	Exon 12 of 13	5		ENSP00000418385.1	C9J6P4
ZC3HAV1	ENST00000680309.1 link	c.1982T>G	p.Leu661Arg	missense_variant	Exon 12 of 13			ENSP00000505045.1	A0A7P0T8C6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242430

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000351

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1450244

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000238

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2417T>G (p.L806R) alteration is located in exon 12 (coding exon 12) of the ZC3HAV1 gene. This alteration results from a T to G substitution at nucleotide position 2417, causing the leucine (L) at amino acid position 806 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.34

CADD

Benign

2.2

DANN

Benign

0.95

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.18

Sift

Benign

0.032

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.87

P;.

Vest4

0.52

MutPred

0.65

Gain of disorder (P = 0.0229);.;

MVP

0.072

MPC

0.41

ClinPred

0.72

GERP RS

-0.60

Varity_R

0.41

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over