7-139061110-TTT-CTC

Variant names:

• chr7-139061110-TTT-CTC
• NM_020119.4:c.2020_2022delAAAinsGAG
• ZC3HAV1 p.Lys674Glu

Variant summary

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

The NM_020119.4(ZC3HAV1):​c.2020_2022delAAAinsGAG​(p.Lys674Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• 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.

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.2020_2022delAAAinsGAG	p.Lys674Glu	missense	N/A	NP_064504.2
	ZC3HAV1	NM_001363491.2		c.2386_2388delAAAinsGAG	p.Lys796Glu	missense	N/A	NP_001350420.1	C9J6P4
	ZC3HAV1	NM_024625.4		c.2020_2022delAAAinsGAG	p.Lys674Glu	missense	N/A	NP_078901.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3HAV1	ENST00000242351.10	TSL:1 MANE Select	c.2020_2022delAAAinsGAG	p.Lys674Glu	missense	N/A	ENSP00000242351.5	Q7Z2W4-1
	ZC3HAV1	ENST00000471652.1	TSL:1	c.2020_2022delAAAinsGAG	p.Lys674Glu	missense	N/A	ENSP00000419855.1	Q7Z2W4-2
	ZC3HAV1	ENST00000460845.5	TSL:1	c.712_714delAAAinsGAG	p.Lys238Glu	missense	N/A	ENSP00000420107.1	H7C5K1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-138745856;