NM_030776.3:c.262G>C

Variant names:

• chr20-57615578-C-G
• rs2073145
• NM_030776.3:c.262G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZBP1 NM_030776.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 38 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBP1	NM_030776.3	MANE Select	c.262G>C	p.Glu88Gln	missense splice_region	Exon 3 of 8	NP_110403.2	Q9H171-1
	ZBP1	NM_001160417.2		c.262G>C	p.Glu88Gln	missense splice_region	Exon 3 of 8	NP_001153889.1
	ZBP1	NM_001160418.2		c.37G>C	p.Glu13Gln	missense splice_region	Exon 2 of 7	NP_001153890.1	Q9H171-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBP1	ENST00000371173.8	TSL:1 MANE Select	c.262G>C	p.Glu88Gln	missense splice_region	Exon 3 of 8	ENSP00000360215.3	Q9H171-1
	ZBP1	ENST00000395822.7	TSL:2	c.37G>C	p.Glu13Gln	missense splice_region	Exon 2 of 7	ENSP00000379167.3	Q9H171-7
	ZBP1	ENST00000857154.1		c.37G>C	p.Glu13Gln	missense splice_region	Exon 2 of 7	ENSP00000527213.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 98540

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.49	N
PhyloP100		-0.39
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.034
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.031	B
Vest4		0.022
MutPred		0.063		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2073145; hg19: chr20-56190634;