16-1998546-C-T

Position:

• chr16-1998546-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001405664.1(ZNF598):​c.2431G>A​(p.Asp811Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF598 NM_001405664.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35194466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF598	NM_001405664.1	c.2431G>A	p.Asp811Asn	missense_variant	14/14		NP_001392593.1
ZNF598	NM_178167.5	c.2401G>A	p.Asp801Asn	missense_variant	14/14		NP_835461.2
ZNF598	NM_001405665.1	c.2383G>A	p.Asp795Asn	missense_variant	14/14		NP_001392594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF598	ENST00000562103.2	c.2401G>A	p.Asp801Asn	missense_variant	14/14	1		ENSP00000455308.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Apr 24, 2023

The c.2401G>A (p.D801N) alteration is located in exon 12 (coding exon 12) of the ZNF598 gene. This alteration results from a G to A substitution at nucleotide position 2401, causing the aspartic acid (D) at amino acid position 801 to be replaced by an asparagine (N). 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	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.2	N;N
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.0070	D;D
Vest4		0.26
MVP		0.41
ClinPred		0.88	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2048547;