chr16-2008517-A-T

Position:

• chr16-2008517-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000562103.2(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 ENST00000562103.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF598	NM_178167.5	c.222+1007T>A		intron_variant		ENST00000710288.1	NP_835461.2
ZNF598	NM_001405665.1	c.222+1007T>A		intron_variant			NP_001392594.1
ZNF598	NM_001405664.1	c.222+1007T>A		intron_variant			NP_001392593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF598	ENST00000562103.2	c.222+1007T>A		intron_variant		1		ENSP00000455308	P1

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

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.435

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs757601; hg19: chr16-2058518;