1-15943499-C-G

Position:

• chr1-15943499-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_003443.3(ZBTB17):​c.1597G>C​(p.Val533Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB17 NM_003443.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.781

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZBTB17
• BP4: Computational evidence support a benign effect (MetaRNN=0.092409045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB17	NM_003443.3	c.1597G>C	p.Val533Leu	missense_variant	12/16	ENST00000375743.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB17	ENST00000375743.9	c.1597G>C	p.Val533Leu	missense_variant	12/16	1	NM_003443.3	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Feb 06, 2023

The c.1597G>C (p.V533L) alteration is located in exon 12 (coding exon 10) of the ZBTB17 gene. This alteration results from a G to C substitution at nucleotide position 1597, causing the valine (V) at amino acid position 533 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.75
DEOGEN2	Benign	0.096	T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.19	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.21
MutPred		0.27		Gain of ubiquitination at K537 (P = 0.1181);.;Gain of ubiquitination at K537 (P = 0.1181);
MVP		0.16
MPC		1.5
ClinPred		0.10	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16269994;