7-139055248-C-T

Variant names:

• chr7-139055248-C-T
• rs148135153
• NM_020119.4:c.2144G>A

Variant summary

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

The NM_020119.4(ZC3HAV1):​c.2144G>A​(p.Arg715His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,212 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R715C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.65
• Publications: 5 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=0.0143125355).

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.2144G>A	p.Arg715His	missense	Exon 10 of 13	NP_064504.2
	ZC3HAV1	NM_001363491.2		c.2510G>A	p.Arg837His	missense	Exon 10 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.2144G>A	p.Arg715His	missense	Exon 10 of 13	ENSP00000242351.5	Q7Z2W4-1
	ZC3HAV1	ENST00000464606.5	TSL:5	c.2510G>A	p.Arg837His	missense	Exon 10 of 13	ENSP00000418385.1	C9J6P4
	ZC3HAV1	ENST00000680309.1		c.1709G>A	p.Arg570His	missense	Exon 10 of 13	ENSP00000505045.1	A0A7P0T8C6

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000651

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 250888 AF XY: 0.000133

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 180 AN: 1460982 Hom.: 1 Cov.: 30 AF XY: 0.000128 AC XY: 93 AN XY: 726728

African (AFR) AF: 0.000329 AC: 11 AN: 33474

American (AMR) AF: 0.000269 AC: 12 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86010

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1111518

Other (OTH) AF: 0.000215 AC: 13 AN: 60370

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152230 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74368

African (AFR) AF: 0.000651 AC: 27 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68044

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.000351

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

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	0.076
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.046
DANN	Benign	0.58
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.7
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.0090
Sift	Benign	0.21	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.021
MVP		0.014
MPC		0.43
ClinPred		0.0095	T
GERP RS		-7.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.26
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148135153; hg19: chr7-138739994; COSMIC: COSV54295236;