chr16-1999768-C-T

Variant names:

• chr16-1999768-C-T
• rs1326535902
• NM_178167.5:c.1781G>A

Variant summary

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

The NM_178167.5(ZNF598):​c.1781G>A​(p.Gly594Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,448,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF598 NM_178167.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• 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]

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.1781G>A	p.Gly594Asp	missense	Exon 11 of 14	NP_835461.2	A0AAG2UWE8
	ZNF598	NM_001405664.1		c.1811G>A	p.Gly604Asp	missense	Exon 11 of 14	NP_001392593.1
	ZNF598	NM_001405665.1		c.1763G>A	p.Gly588Asp	missense	Exon 11 of 14	NP_001392594.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF598	ENST00000562103.2	TSL:1	c.1781G>A	p.Gly594Asp	missense	Exon 11 of 14	ENSP00000455308.2	H3BPG6
	ZNF598	ENST00000562988.5	TSL:5	n.1870G>A		non_coding_transcript_exon	Exon 8 of 11
	ZNF598	ENST00000564556.1	TSL:3	n.302G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000456128.1	H3BR87

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448674 Hom.: 0 Cov.: 59 AF XY: 0.00000139 AC XY: 1 AN XY: 721172

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111624

Other (OTH) AF: 0.00 AC: 0 AN: 60246

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.0	T
PhyloP100		5.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.2	N
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.036	D
Vest4		0.63
MVP		0.59
ClinPred		0.86	D
GERP RS		4.4
Mutation Taster		=90/10	polymorphism

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: rs1326535902; hg19: chr16-2049769;