7-139073929-T-A

Variant names:

• chr7-139073929-T-A
• NM_020119.4:c.1799A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020119.4(ZC3HAV1):​c.1799A>T​(p.Asn600Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.187
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19319013).

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.1799A>T	p.Asn600Ile	missense	Exon 7 of 13	NP_064504.2
	ZC3HAV1	NM_001363491.2		c.2165A>T	p.Asn722Ile	missense	Exon 7 of 13	NP_001350420.1	C9J6P4
	ZC3HAV1	NM_024625.4		c.1799A>T	p.Asn600Ile	missense	Exon 7 of 9	NP_078901.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1	ENST00000242351.10	TSL:1 MANE Select	c.1799A>T	p.Asn600Ile	missense	Exon 7 of 13	ENSP00000242351.5	Q7Z2W4-1
	ZC3HAV1	ENST00000471652.1	TSL:1	c.1799A>T	p.Asn600Ile	missense	Exon 7 of 9	ENSP00000419855.1	Q7Z2W4-2
	ZC3HAV1	ENST00000460845.5	TSL:1	c.491A>T	p.Asn164Ile	missense	Exon 4 of 6	ENSP00000420107.1	H7C5K1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.19
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.052
Sift	Benign	0.057	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.88	P
Vest4		0.26
MutPred		0.37		Loss of disorder (P = 0.0406)
MVP		0.048
MPC		1.1
ClinPred		0.93	D
GERP RS		-5.5
Varity_R		0.42
gMVP		0.60
Mutation Taster		=93/7	polymorphism

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

hg19: chr7-138758675;