20-57615578-C-G

Position:

• chr20-57615578-C-G

Variant summary

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

The NM_030776.3(ZBP1):​c.262G>C​(p.Glu88Gln) variant causes a missense, splice region 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. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E88K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZBP1 NM_030776.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

Genes affected

ZBP1 (HGNC:16176): (Z-DNA binding protein 1) This gene encodes a Z-DNA binding protein. The encoded protein plays a role in the innate immune response by binding to foreign DNA and inducing type-I interferon production. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

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/exons	MANE	UniProt
ZBP1	NM_030776.3	c.262G>C	p.Glu88Gln	missense_variant, splice_region_variant	3/8	ENST00000371173.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBP1	ENST00000371173.8	c.262G>C	p.Glu88Gln	missense_variant, splice_region_variant	3/8	1	NM_030776.3	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0053	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N;.;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.031	B;.;.
Vest4		0.022
MutPred		0.063		Gain of loop (P = 0.1069);.;Gain of loop (P = 0.1069);
MVP		0.21
MPC		0.045
ClinPred		0.042	T
GERP RS		-1.1
Varity_R		0.036
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073145; hg19: chr20-56190634;