9-126880459-C-T

Position:

• chr9-126880459-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099270.4(ZBTB34):​c.1060C>T​(p.Pro354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZBTB34 NM_001099270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49

Genes affected

ZBTB34 (HGNC:31446): (zinc finger and BTB domain containing 34) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10072833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB34	NM_001099270.4	c.1060C>T	p.Pro354Ser	missense_variant	2/2	ENST00000319119.5	NP_001092740.2
ZBTB34	NM_001395198.1	c.1090C>T	p.Pro364Ser	missense_variant	3/3		NP_001382127.1
ZBTB34	XM_047423402.1	c.1090C>T	p.Pro364Ser	missense_variant	3/3		XP_047279358.1
ZBTB34	XM_011518699.4	c.1060C>T	p.Pro354Ser	missense_variant	2/2		XP_011517001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5	c.1060C>T	p.Pro354Ser	missense_variant	2/2	1	NM_001099270.4	ENSP00000317534.4
ZBTB34	ENST00000695642.1	c.1090C>T	p.Pro364Ser	missense_variant	3/3			ENSP00000512077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461410 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726978

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 07, 2024

The c.1048C>T (p.P350S) alteration is located in exon 2 (coding exon 1) of the ZBTB34 gene. This alteration results from a C to T substitution at nucleotide position 1048, causing the proline (P) at amino acid position 350 to be replaced by a serine (S). 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	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.49
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.039
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	.;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	0.97	T;T
Polyphen		0.018	.;B
Vest4		0.26
MutPred		0.17		.;Gain of phosphorylation at P350 (P = 0.0222);
MVP		0.082
MPC		0.75
ClinPred		0.41	T
GERP RS		5.9
Varity_R		0.095
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-129642738;