1-15944343-T-C

Position:

• chr1-15944343-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Moderate BS2

The NM_003443.3(ZBTB17):​c.1328A>G​(p.Asp443Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000427 in 1,404,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: ZBTB17 NM_003443.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

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 Likely_benign. Variant got -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ZBTB17
• BP4: Computational evidence support a benign effect (MetaRNN=0.20993036).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB17	NM_003443.3	c.1328A>G	p.Asp443Gly	missense_variant	9/16	ENST00000375743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB17	ENST00000375743.9	c.1328A>G	p.Asp443Gly	missense_variant	9/16	1	NM_003443.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000427 AC: 6 AN: 1404286 Hom.: 0 Cov.: 31 AF XY: 0.00000577 AC XY: 4 AN XY: 693318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000554

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1328A>G (p.D443G) alteration is located in exon 9 (coding exon 7) of the ZBTB17 gene. This alteration results from a A to G substitution at nucleotide position 1328, causing the aspartic acid (D) at amino acid position 443 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;.;.
Eigen	Benign	0.0030
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N;.;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Benign	0.076
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.0010	B;.;B
Vest4		0.27
MutPred		0.31		Loss of stability (P = 0.0303);.;Loss of stability (P = 0.0303);
MVP		0.31
MPC		1.6
ClinPred		0.93	D
GERP RS		3.1
Varity_R		0.42
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1350282418; hg19: chr1-16270838;