rs9661939

Variant names:

• chr1-15944765-G-A
• rs9661939
• NM_003443.3:c.1002C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003443.3(ZBTB17):​c.1002C>T​(p.Phe334Phe) 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 NM_003443.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.87
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003443.3. 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
	ZBTB17	NM_003443.3	MANE Select	c.1002C>T	p.Phe334Phe	synonymous	Exon 8 of 16	NP_003434.2	Q13105-1
	ZBTB17	NM_001287603.2		c.1002C>T	p.Phe334Phe	synonymous	Exon 8 of 16	NP_001274532.1	Q13105-2
	ZBTB17	NM_001324138.2		c.813C>T	p.Phe271Phe	synonymous	Exon 7 of 15	NP_001311067.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB17	ENST00000375743.9	TSL:1 MANE Select	c.1002C>T	p.Phe334Phe	synonymous	Exon 8 of 16	ENSP00000364895.4	Q13105-1
	ZBTB17	ENST00000375733.6	TSL:1	c.1002C>T	p.Phe334Phe	synonymous	Exon 8 of 16	ENSP00000364885.2	Q13105-2
	ZBTB17	ENST00000894624.1		c.1002C>T	p.Phe334Phe	synonymous	Exon 7 of 15	ENSP00000564683.1

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

GnomAD2 exomes AF: 0.285 AC: 69731 AN: 244386 AF XY: 0.297

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 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

African (AFR) AF: 0.103 AC: 3443 AN: 33472

American (AMR) AF: 0.325 AC: 14495 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9438 AN: 26106

East Asian (EAS) AF: 0.0107 AC: 423 AN: 39670

South Asian (SAS) AF: 0.426 AC: 36697 AN: 86174

European-Finnish (FIN) AF: 0.228 AC: 11961 AN: 52462

Middle Eastern (MID) AF: 0.357 AC: 2057 AN: 5766

European-Non Finnish (NFE) AF: 0.298 AC: 331265 AN: 1111546

Other (OTH) AF: 0.283 AC: 17062 AN: 60336

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

African (AFR) AF: 0.109 AC: 4544 AN: 41572

American (AMR) AF: 0.294 AC: 4489 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3470

East Asian (EAS) AF: 0.0153 AC: 79 AN: 5170

South Asian (SAS) AF: 0.422 AC: 2037 AN: 4828

European-Finnish (FIN) AF: 0.239 AC: 2533 AN: 10608

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20466 AN: 67962

Other (OTH) AF: 0.265 AC: 560 AN: 2116

Alfa AF: 0.280 Hom.: 3096

Bravo AF: 0.233

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		4.9
PromoterAI		0.028	Neutral
Mutation Taster		=81/19	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: rs9661939; hg19: chr1-16271260;