16-88577634-G-A

Position:

• chr16-88577634-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144604.4(ZC3H18):​c.511G>A​(p.Val171Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZC3H18 NM_144604.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054251432).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H18	NM_144604.4	c.511G>A	p.Val171Ile	missense_variant	2/18	ENST00000301011.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H18	ENST00000301011.10	c.511G>A	p.Val171Ile	missense_variant	2/18	1	NM_144604.4	P1
ZC3H18	ENST00000452588.6	c.511G>A	p.Val171Ile	missense_variant	2/19	2
ZC3H18	ENST00000569435.5	c.252+259G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461670 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.93
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.044
Sift	Benign	0.13	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0090	B;B
Vest4		0.040
MVP		0.043
MPC		0.017
ClinPred		0.027	T
GERP RS		3.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.022
gMVP		0.0082

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

Publications

LitVar

Other links and lift over

dbSNP: rs372875401; hg19: chr16-88644042;