9-126880511-C-A

Position:

• chr9-126880511-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099270.4(ZBTB34):​c.1112C>A​(p.Pro371Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB34 NM_001099270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4222972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB34	NM_001099270.4	c.1112C>A	p.Pro371Gln	missense_variant	2/2	ENST00000319119.5	NP_001092740.2
ZBTB34	NM_001395198.1	c.1142C>A	p.Pro381Gln	missense_variant	3/3		NP_001382127.1
ZBTB34	XM_047423402.1	c.1142C>A	p.Pro381Gln	missense_variant	3/3		XP_047279358.1
ZBTB34	XM_011518699.4	c.1112C>A	p.Pro371Gln	missense_variant	2/2		XP_011517001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5	c.1112C>A	p.Pro371Gln	missense_variant	2/2	1	NM_001099270.4	ENSP00000317534.4
ZBTB34	ENST00000695642.1	c.1142C>A	p.Pro381Gln	missense_variant	3/3			ENSP00000512077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 09, 2023

The c.1100C>A (p.P367Q) alteration is located in exon 2 (coding exon 1) of the ZBTB34 gene. This alteration results from a C to A substitution at nucleotide position 1100, causing the proline (P) at amino acid position 367 to be replaced by a glutamine (Q). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.17
Sift	Benign	0.082	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.94	.;P
Vest4		0.57
MutPred		0.51		.;Loss of loop (P = 0.0203);
MVP		0.082
MPC		0.84
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.11
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-129642790; COSMIC: COSV105900206;