dbSNP rs3735007: ZC3HAV1:p.Thr851Ile (chr7-139047751-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020119.4(ZC3HAV1):c.2552C>T(p.Thr851Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,612,984 control chromosomes in the GnomAD database, including 212,893 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.55 ( 23913 hom., cov: 32)

Exomes 𝑓: 0.50 ( 188980 hom. )

Consequence

ZC3HAV1
NM_020119.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.535

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6139737E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4 link	c.2552C>T	p.Thr851Ile	missense_variant	Exon 13 of 13	ENST00000242351.10	NP_064504.2	Q7Z2W4-1
ZC3HAV1	NM_001363491.2 link	c.2918C>T	p.Thr973Ile	missense_variant	Exon 13 of 13		NP_001350420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZC3HAV1	ENST00000242351.10 link	c.2552C>T	p.Thr851Ile	missense_variant	Exon 13 of 13	1	NM_020119.4	ENSP00000242351.5	Q7Z2W4-1
ZC3HAV1	ENST00000464606.5 link	c.2918C>T	p.Thr973Ile	missense_variant	Exon 13 of 13	5		ENSP00000418385.1	C9J6P4
ZC3HAV1	ENST00000680309.1 link	c.2117C>T	p.Thr706Ile	missense_variant	Exon 13 of 13			ENSP00000505045.1	A0A7P0T8C6

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

83755

AN:

151894

Hom.:

23879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.496

AC:

124633

AN:

251216

Hom.:

32112

AF XY:

0.501

AC XY:

68034

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.701

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.353

Gnomad SAS exome

AF:

0.551

Gnomad FIN exome

AF:

0.547

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.508

GnomAD4 exome

AF:

0.505

AC:

737188

AN:

1460972

Hom.:

188980

Cov.:

AF XY:

0.507

AC XY:

368239

AN XY:

726850

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.553

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.503

Gnomad4 OTH exome

AF:

0.504

GnomAD4 genome

AF:

0.551

AC:

83833

AN:

152012

Hom.:

23913

Cov.:

AF XY:

0.549

AC XY:

40788

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.583

Gnomad4 EAS

AF:

0.348

Gnomad4 SAS

AF:

0.563

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.514

Gnomad4 OTH

AF:

0.529

Alfa

AF:

0.515

Hom.:

36405

Bravo

AF:

0.541

TwinsUK

AF:

0.503

AC:

1864

ALSPAC

AF:

0.502

AC:

1933

ESP6500AA

AF:

0.703

AC:

3097

ESP6500EA

AF:

0.519

AC:

4460

ExAC

AF:

0.506

AC:

61390

Asia WGS

AF:

0.453

AC:

1575

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0050

DANN

Benign

0.84

DEOGEN2

Benign

0.0060

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0000026

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.23

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.068

Sift

Benign

1.0

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;.

Vest4

0.046

MPC

0.31

ClinPred

0.0084

GERP RS

-6.0

Varity_R

0.033

gMVP

0.39

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over