chr7-139054052-C-T

Variant names:

• chr7-139054052-C-T
• rs1003122409
• NM_020119.4:c.2231G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020119.4(ZC3HAV1):​c.2231G>A​(p.Ser744Asn) 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. 14/21 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: 0.452

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13947377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3HAV1	NM_020119.4	c.2231G>A	p.Ser744Asn	missense_variant	Exon 11 of 13	ENST00000242351.10	NP_064504.2
ZC3HAV1	NM_001363491.2	c.2597G>A	p.Ser866Asn	missense_variant	Exon 11 of 13		NP_001350420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HAV1	ENST00000242351.10	c.2231G>A	p.Ser744Asn	missense_variant	Exon 11 of 13	1	NM_020119.4	ENSP00000242351.5
ZC3HAV1	ENST00000464606.5	c.2597G>A	p.Ser866Asn	missense_variant	Exon 11 of 13	5		ENSP00000418385.1
ZC3HAV1	ENST00000680309.1	c.1796G>A	p.Ser599Asn	missense_variant	Exon 11 of 13			ENSP00000505045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2231G>A (p.S744N) alteration is located in exon 11 (coding exon 11) of the ZC3HAV1 gene. This alteration results from a G to A substitution at nucleotide position 2231, causing the serine (S) at amino acid position 744 to be replaced by an asparagine (N). 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	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.0046	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.060
Sift	Benign	0.51	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.93	P;.
Vest4		0.14
MutPred		0.45		Loss of phosphorylation at S744 (P = 0.0464);.;
MVP		0.081
MPC		0.27
ClinPred		0.27	T
GERP RS		2.7
Varity_R		0.20
gMVP		0.63

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: rs1003122409; hg19: chr7-138738798;