9-126884496-A-G

Position:

• chr9-126884496-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099270.4(ZBTB34):​c.*3582A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 166,050 control chromosomes in the GnomAD database, including 1,772 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1594 hom., cov: 32)
  • Exomes 𝑓: 0.16 (178 hom.)
• Consequence: ZBTB34 NM_001099270.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB34	NM_001099270.4	c.*3582A>G		3_prime_UTR_variant	2/2	ENST00000319119.5	NP_001092740.2
ZBTB34	NM_001395198.1	c.*3582A>G		3_prime_UTR_variant	3/3		NP_001382127.1
ZBTB34	XM_047423402.1	c.*3582A>G		3_prime_UTR_variant	3/3		XP_047279358.1
ZBTB34	XM_011518699.4	c.*3582A>G		3_prime_UTR_variant	2/2		XP_011517001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5	c.*3582A>G		3_prime_UTR_variant	2/2	1	NM_001099270.4	ENSP00000317534.4
ZBTB34	ENST00000695642.1	c.*3582A>G		3_prime_UTR_variant	3/3			ENSP00000512077.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17669 AN: 151232 Hom.: 1598 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.0945

GnomAD4 exome AF: 0.157 AC: 2311 AN: 14704 Hom.: 178 Cov.: 0 AF XY: 0.156 AC XY: 1086 AN XY: 6968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.0930

GnomAD4 genome AF: 0.117 AC: 17672 AN: 151346 Hom.: 1594 Cov.: 32 AF XY: 0.124 AC XY: 9184 AN XY: 73894

Gnomad4 AFR AF: 0.0925

Gnomad4 AMR AF: 0.0950

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0943

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.0923 Hom.: 1052

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.035
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs12178; hg19: chr9-129646775;