16-88598656-C-A

Variant names:

• chr16-88598656-C-A
• rs746214348
• NM_144604.4:c.874C>A

Variant summary

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

The NM_144604.4(ZC3H18):​c.874C>A​(p.Pro292Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P292A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC3H18 NM_144604.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• Publications: 1 publications found

Genes affected

ZC3H18 (HGNC:25091): (zinc finger CCCH-type containing 18) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in RNA destabilization. Located in nuclear speck. Part of ribonucleoprotein complex. [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=0.25064743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H18	NM_144604.4	c.874C>A	p.Pro292Thr	missense_variant	Exon 5 of 18	ENST00000301011.10	NP_653205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H18	ENST00000301011.10	c.874C>A	p.Pro292Thr	missense_variant	Exon 5 of 18	1	NM_144604.4	ENSP00000301011.5
ZC3H18	ENST00000452588.6	c.946C>A	p.Pro316Thr	missense_variant	Exon 6 of 19	2		ENSP00000416951.2
ZC3H18	ENST00000567085.1	c.253C>A	p.Pro85Thr	missense_variant	Exon 3 of 6	5		ENSP00000455083.1
ZC3H18	ENST00000569435.5	c.523C>A	p.Pro175Thr	missense_variant	Exon 5 of 6	5		ENSP00000455260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L;.;.
PhyloP100		4.3
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.15
Sift	Benign	0.035	D;D;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.48
MutPred		0.24		.;Gain of phosphorylation at P316 (P = 0.0086);.;
MVP		0.043
MPC		0.40
ClinPred		0.87	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.64

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: rs746214348; hg19: chr16-88665064;