chr7-139047751-G-A

Variant names:

• chr7-139047751-G-A
• rs3735007
• NM_020119.4:c.2552C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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	c.2552C>T	p.Thr851Ile	missense_variant	Exon 13 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	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	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.2552C>T	p.Thr851Ile	missense_variant	Exon 13 of 13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000464606.5	c.2918C>T	p.Thr973Ile	missense_variant	Exon 13 of 13	5		ENSP00000418385.1
ZC3HAV1	ENST00000680309.1	c.2117C>T	p.Thr706Ile	missense_variant	Exon 13 of 13			ENSP00000505045.1

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

GnomAD2 exomes AF: 0.496 AC: 124633 AN: 251216 AF XY: 0.501

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 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

African (AFR) AF: 0.713 AC: 23876 AN: 33468

American (AMR) AF: 0.340 AC: 15206 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 15064 AN: 26122

East Asian (EAS) AF: 0.349 AC: 13836 AN: 39694

South Asian (SAS) AF: 0.553 AC: 47666 AN: 86200

European-Finnish (FIN) AF: 0.537 AC: 28648 AN: 53386

Middle Eastern (MID) AF: 0.589 AC: 3396 AN: 5762

European-Non Finnish (NFE) AF: 0.503 AC: 559037 AN: 1111278

Other (OTH) AF: 0.504 AC: 30459 AN: 60380

GnomAD4 genome AF: 0.551 AC: 83833 AN: 152012 Hom.: 23913 Cov.: 32 AF XY: 0.549 AC XY: 40788 AN XY: 74284

African (AFR) AF: 0.696 AC: 28870 AN: 41466

American (AMR) AF: 0.388 AC: 5923 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1801 AN: 5176

South Asian (SAS) AF: 0.563 AC: 2716 AN: 4822

European-Finnish (FIN) AF: 0.544 AC: 5735 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34934 AN: 67954

Other (OTH) AF: 0.529 AC: 1116 AN: 2108

Alfa AF: 0.524 Hom.: 55293

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;.
PhyloP100		-0.54
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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