7-139064992-T-C

Variant names:

• chr7-139064992-T-C
• NM_020119.4:c.1880A>G

Variant summary

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

The NM_020119.4(ZC3HAV1):​c.1880A>G​(p.Lys627Arg) 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. 15/21 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: -0.360

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=0.049862772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.1880A>G	p.Lys627Arg	missense_variant	Exon 8 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.2246A>G	p.Lys749Arg	missense_variant	Exon 8 of 13		NP_001350420.1
ZC3HAV1	NM_024625.4	c.1880A>G	p.Lys627Arg	missense_variant	Exon 8 of 9		NP_078901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.1880A>G	p.Lys627Arg	missense_variant	Exon 8 of 13	1	NM_020119.4	ENSP00000242351.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1880A>G (p.K627R) alteration is located in exon 8 (coding exon 8) of the ZC3HAV1 gene. This alteration results from a A to G substitution at nucleotide position 1880, causing the lysine (K) at amino acid position 627 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.6
DANN	Benign	0.92
DEOGEN2	Benign	0.0011	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.065	N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.037	B;.;B
Vest4		0.14
MutPred		0.37		Loss of methylation at K627 (P = 0.0097);.;Loss of methylation at K627 (P = 0.0097);
MVP		0.030
MPC		0.24
ClinPred		0.036	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-138749738;