NM_032494.3:c.483G>T

Variant names:

• chr2-112236583-C-A
• NM_032494.3:c.483G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032494.3(ZC3H8):​c.483G>T​(p.Arg161Ser) 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. 15/22 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: ZC3H8 NM_032494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.604
• Publications: 0 publications found

Genes affected

ZC3H8 (HGNC:30941): (zinc finger CCCH-type containing 8) Enables RNA binding activity. Involved in several processes, including positive regulation of thymocyte apoptotic process; regulation of transcription, DNA-templated; and snRNA transcription. Located in Cajal body; histone locus body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

FBLN7 (HGNC:26740): (fibulin 7) Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of biomineralization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05208847).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032494.3. 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
	ZC3H8	NM_032494.3	MANE Select	c.483G>T	p.Arg161Ser	missense	Exon 4 of 9	NP_115883.2	Q8N5P1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC3H8	ENST00000409573.7	TSL:5 MANE Select	c.483G>T	p.Arg161Ser	missense	Exon 4 of 9	ENSP00000386488.1	Q8N5P1
	ZC3H8	ENST00000866700.1		c.483G>T	p.Arg161Ser	missense	Exon 4 of 9	ENSP00000536759.1
	ZC3H8	ENST00000866701.1		c.483G>T	p.Arg161Ser	missense	Exon 4 of 8	ENSP00000536760.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.60
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.0050
Sift	Benign	0.51	T
Sift4G	Benign	0.73	T
Polyphen		0.041	B
Vest4		0.14
MutPred		0.25		Loss of MoRF binding (P = 0.0156)
MVP		0.067
MPC		0.19
ClinPred		0.048	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.37
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr2-112994160;