7-139054073-T-C

Variant names:

• chr7-139054073-T-C
• rs775926377
• NM_020119.4:c.2210A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020119.4(ZC3HAV1):​c.2210A>G​(p.His737Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,584,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.914
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05868393).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1	NM_020119.4	MANE Select	c.2210A>G	p.His737Arg	missense	Exon 11 of 13	NP_064504.2
	ZC3HAV1	NM_001363491.2		c.2576A>G	p.His859Arg	missense	Exon 11 of 13	NP_001350420.1	C9J6P4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1	ENST00000242351.10	TSL:1 MANE Select	c.2210A>G	p.His737Arg	missense	Exon 11 of 13	ENSP00000242351.5	Q7Z2W4-1
	ZC3HAV1	ENST00000464606.5	TSL:5	c.2576A>G	p.His859Arg	missense	Exon 11 of 13	ENSP00000418385.1	C9J6P4
	ZC3HAV1	ENST00000680309.1		c.1775A>G	p.His592Arg	missense	Exon 11 of 13	ENSP00000505045.1	A0A7P0T8C6

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000181 AC: 40 AN: 220764 AF XY: 0.000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000399

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.000110 AC: 157 AN: 1432568 Hom.: 0 Cov.: 31 AF XY: 0.0000969 AC XY: 69 AN XY: 712258

African (AFR) AF: 0.00 AC: 0 AN: 31186

American (AMR) AF: 0.0000283 AC: 1 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25248

East Asian (EAS) AF: 0.00 AC: 0 AN: 38674

South Asian (SAS) AF: 0.00 AC: 0 AN: 79982

European-Finnish (FIN) AF: 0.0000566 AC: 3 AN: 53002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.000139 AC: 153 AN: 1104180

Other (OTH) AF: 0.00 AC: 0 AN: 59236

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.0000482 AC: 2 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000196 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.000247 AC: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.40
DANN	Benign	0.50
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.91
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.058
Sift	Benign	0.18	T
Sift4G	Benign	0.30	T
Polyphen		0.30	B
Vest4		0.095
MutPred		0.49		Gain of solvent accessibility (P = 0.1133)
MVP		0.014
MPC		0.45
ClinPred		0.056	T
GERP RS		-9.1
Varity_R		0.29
gMVP		0.60
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs775926377; hg19: chr7-138738819;