16-1998986-G-A

Position:

• chr16-1998986-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001405664.1(ZNF598):​c.2219C>T​(p.Ala740Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,339,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ZNF598 NM_001405664.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

Genes affected

ZNF598 (HGNC:28079): (zinc finger protein 598, E3 ubiquitin ligase) Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This protein and Grb10-interacting GYF protein 2 have been identified as a components of the mammalian 4EHP (m4EHP) complex. The complex is thought to function as a translation repressor in embryonic development. [provided by RefSeq, Oct 2012]

ZNF598 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058740437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF598	NM_001405664.1	c.2219C>T	p.Ala740Val	missense_variant	12/14		NP_001392593.1
ZNF598	NM_178167.5	c.2189C>T	p.Ala730Val	missense_variant	12/14		NP_835461.2
ZNF598	NM_001405665.1	c.2171C>T	p.Ala724Val	missense_variant	12/14		NP_001392594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF598	ENST00000562103.2	c.2189C>T	p.Ala730Val	missense_variant	12/14	1		ENSP00000455308.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.47e-7 AC: 1 AN: 1339244 Hom.: 0 Cov.: 35 AF XY: 0.00000153 AC XY: 1 AN XY: 652656

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: 9.54e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2022

The c.2189C>T (p.A730V) alteration is located in exon 10 (coding exon 10) of the ZNF598 gene. This alteration results from a C to T substitution at nucleotide position 2189, causing the alanine (A) at amino acid position 730 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.3
DANN	Benign	0.56
DEOGEN2	Benign	0.0048	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.39	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.21	N;N
Sift	Benign	1.0	T;T
Sift4G	Benign	0.32	T;T
Vest4		0.059
MVP		0.31
ClinPred		0.053	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2048987;