8-143441035-C-G

Variant names:

• chr8-143441035-C-G
• rs368841712
• NM_015117.3:c.2393G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015117.3(ZC3H3):​c.2393G>C​(p.Arg798Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,334,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R798H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ZC3H3 NM_015117.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

Genes affected

ZC3H3 (HGNC:28972): (zinc finger CCCH-type containing 3) Predicted to enable SMAD binding activity. Involved in regulation of mRNA polyadenylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1650449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H3	NM_015117.3	c.2393G>C	p.Arg798Pro	missense_variant	Exon 10 of 12	ENST00000262577.6	NP_055932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H3	ENST00000262577.6	c.2393G>C	p.Arg798Pro	missense_variant	Exon 10 of 12	1	NM_015117.3	ENSP00000262577.5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1334168 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 658144

African (AFR) AF: 0.00 AC: 0 AN: 26370

American (AMR) AF: 0.00 AC: 0 AN: 21374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21086

East Asian (EAS) AF: 0.00 AC: 0 AN: 31756

South Asian (SAS) AF: 0.00 AC: 0 AN: 68102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5376

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1059992

Other (OTH) AF: 0.00 AC: 0 AN: 54936

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.14
Sift	Benign	0.27	T
Sift4G	Benign	0.25	T
Polyphen		0.36	B
Vest4		0.44
MutPred		0.31		Loss of MoRF binding (P = 0.01);
MVP		0.11
ClinPred		0.77	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.74
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs368841712; hg19: chr8-144523205;