rs9661939

Positions:

• chr1-15944765-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000375743.9(ZBTB17):​c.1002C>T​(p.Phe334=) variant causes a synonymous change. The variant allele was found at a frequency of 0.287 in 1,612,314 control chromosomes in the GnomAD database, including 71,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5174 hom., cov: 33)
  • Exomes 𝑓: 0.29 (65999 hom.)
• Consequence: ZBTB17 ENST00000375743.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.87

Genes affected

ZBTB17 (HGNC:12936): (zinc finger and BTB domain containing 17) This gene encodes a zinc finger protein involved in the regulation of c-myc. The symbol MIZ1 has also been associated with PIAS2 which is a different gene located on chromosome 18. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-15944765-G-A is Benign according to our data. Variant chr1-15944765-G-A is described in ClinVar as [Benign]. Clinvar id is 1280656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB17	NM_003443.3	c.1002C>T	p.Phe334=	synonymous_variant	8/16	ENST00000375743.9	NP_003434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB17	ENST00000375743.9	c.1002C>T	p.Phe334=	synonymous_variant	8/16	1	NM_003443.3	ENSP00000364895	P2
ZBTB17	ENST00000375733.6	c.1002C>T	p.Phe334=	synonymous_variant	8/16	1		ENSP00000364885	A2
ZBTB17	ENST00000537142.5	c.756C>T	p.Phe252=	synonymous_variant	7/15	2		ENSP00000438529
ZBTB17	ENST00000492834.1	n.711C>T		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36276 AN: 152108 Hom.: 5166 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.285 AC: 69731 AN: 244386 Hom.: 11285 AF XY: 0.297 AC XY: 39320 AN XY: 132540

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.0164

Gnomad SAS exome AF: 0.426

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.303

GnomAD4 exome AF: 0.292 AC: 426841 AN: 1460088 Hom.: 65999 Cov.: 76 AF XY: 0.298 AC XY: 216202 AN XY: 726294

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.239 AC: 36310 AN: 152226 Hom.: 5174 Cov.: 33 AF XY: 0.240 AC XY: 17893 AN XY: 74420

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.265

Alfa AF: 0.280 Hom.: 3096

Bravo AF: 0.233

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.81

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: rs9661939; hg19: chr1-16271260;