chr7-139053483-A-G

Variant names:

• chr7-139053483-A-G
• rs761078215
• NM_020119.4:c.2417T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020119.4(ZC3HAV1):​c.2417T>C​(p.Leu806Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,450,244 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.2417T>C	p.Leu806Pro	missense_variant	Exon 12 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.2783T>C	p.Leu928Pro	missense_variant	Exon 12 of 13		NP_001350420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.2417T>C	p.Leu806Pro	missense_variant	Exon 12 of 13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000464606.5	c.2783T>C	p.Leu928Pro	missense_variant	Exon 12 of 13	5		ENSP00000418385.1
ZC3HAV1	ENST00000680309.1	c.1982T>C	p.Leu661Pro	missense_variant	Exon 12 of 13			ENSP00000505045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1450244 Hom.: 0 Cov.: 30 AF XY: 0.00000416 AC XY: 3 AN XY: 721202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.98	D;.
Vest4		0.36
MutPred		0.68		Gain of disorder (P = 0.0141);.;
MVP		0.085
MPC		0.70
ClinPred		0.85	D
GERP RS		-0.60
Varity_R		0.64
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs761078215; hg19: chr7-138738229; COSMIC: COSV54297690; COSMIC: COSV54297690;