16-2008517-A-T

Variant names:

• chr16-2008517-A-T
• rs757601
• NM_178167.5:c.222+1007T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178167.5(ZNF598):​c.222+1007T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,210 control chromosomes in the GnomAD database, including 17,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17863 hom., cov: 34)
• Consequence: ZNF598 NM_178167.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF598	NM_178167.5	MANE Select	c.222+1007T>A		intron	N/A	NP_835461.2
	ZNF598	NM_001405664.1		c.222+1007T>A		intron	N/A	NP_001392593.1
	ZNF598	NM_001405665.1		c.222+1007T>A		intron	N/A	NP_001392594.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF598	ENST00000562103.2	TSL:1	c.222+1007T>A		intron	N/A	ENSP00000455308.2
	ZNF598	ENST00000562988.5	TSL:5	n.241+1007T>A		intron	N/A
	ZNF598	ENST00000564824.5	TSL:5	n.241+1007T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71286 AN: 152090 Hom.: 17833 Cov.: 34

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.436

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.469 AC: 71370 AN: 152210 Hom.: 17863 Cov.: 34 AF XY: 0.465 AC XY: 34614 AN XY: 74400

African (AFR) AF: 0.652 AC: 27066 AN: 41522

American (AMR) AF: 0.435 AC: 6661 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2038 AN: 5180

South Asian (SAS) AF: 0.329 AC: 1591 AN: 4830

European-Finnish (FIN) AF: 0.389 AC: 4119 AN: 10584

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26974 AN: 68000

Other (OTH) AF: 0.435 AC: 921 AN: 2116

Alfa AF: 0.331 Hom.: 893

Bravo AF: 0.479

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.48
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs757601; hg19: chr16-2058518;