7-139055249-G-T

Variant names:

• chr7-139055249-G-T
• NM_020119.4:c.2143C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020119.4(ZC3HAV1):​c.2143C>A​(p.Arg715Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZC3HAV1 NM_020119.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037171096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.2143C>A	p.Arg715Ser	missense_variant	Exon 10 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.2509C>A	p.Arg837Ser	missense_variant	Exon 10 of 13		NP_001350420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.2143C>A	p.Arg715Ser	missense_variant	Exon 10 of 13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000464606.5	c.2509C>A	p.Arg837Ser	missense_variant	Exon 10 of 13	5		ENSP00000418385.1
ZC3HAV1	ENST00000680309.1	c.1708C>A	p.Arg570Ser	missense_variant	Exon 10 of 13			ENSP00000505045.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460996 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726714

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.27
DANN	Benign	0.56
DEOGEN2	Benign	0.00071	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.017
Sift	Benign	0.20	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0	B;.
Vest4		0.050
MutPred		0.35		Gain of disorder (P = 0.0469);.;
MVP		0.014
MPC		0.34
ClinPred		0.065	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.091
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-138739995;