rs3735007

chr7-139047751-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.55 (23913 hom., cov: 32)
  • Exomes 𝑓: 0.50 (188980 hom.)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

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]

ACMG classification

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/exons	MANE	UniProt
ZC3HAV1	NM_020119.4	c.2552C>T	p.Thr851Ile	missense_variant	13/13	ENST00000242351.10
ZC3HAV1	NM_001363491.2	c.2918C>T	p.Thr973Ile	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.2552C>T	p.Thr851Ile	missense_variant	13/13	1	NM_020119.4	A2
ZC3HAV1	ENST00000464606.5	c.2918C>T	p.Thr973Ile	missense_variant	13/13	5		P2
ZC3HAV1	ENST00000680309.1	c.2117C>T	p.Thr706Ile	missense_variant	13/13

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83755 AN: 151894 Hom.: 23879 Cov.: 32

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

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.: 58 AF XY: 0.507 AC XY: 368239 AN XY: 726850

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.: 32 AF XY: 0.549 AC XY: 40788 AN XY: 74284

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	T
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	N
LIST_S2	Benign	0.28	T;T
MetaRNN	Benign	0.0000026	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.23	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs3735007; hg19: chr7-138732497; COSMIC: COSV54295836; COSMIC: COSV54295836;