16-1998555-T-C

Variant names:

• chr16-1998555-T-C
• NM_178167.5:c.2392A>G

Variant summary

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

The NM_178167.5(ZNF598):​c.2392A>G​(p.Ser798Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF598 NM_178167.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66
• Publications: 0 publications found

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]

ENSG00000260107 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF598	NM_178167.5	MANE Select	c.2392A>G	p.Ser798Gly	missense	Exon 14 of 14	NP_835461.2	A0AAG2UWE8
	ZNF598	NM_001405664.1		c.2422A>G	p.Ser808Gly	missense	Exon 14 of 14	NP_001392593.1
	ZNF598	NM_001405665.1		c.2374A>G	p.Ser792Gly	missense	Exon 14 of 14	NP_001392594.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF598	ENST00000562103.2	TSL:1	c.2392A>G	p.Ser798Gly	missense	Exon 14 of 14	ENSP00000455308.2	H3BPG6
	ZNF598	ENST00000562988.5	TSL:5	n.2481A>G		non_coding_transcript_exon	Exon 11 of 11
	ZNF598	ENST00000564556.1	TSL:3	n.*147A>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000456128.1	H3BR87

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.97	T
PhyloP100		5.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N
Sift	Benign	0.083	T
Sift4G	Uncertain	0.0040	D
Vest4		0.58
MVP		0.48
ClinPred		0.88	D
GERP RS		5.3

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

hg19: chr16-2048556;