Genetic Variant NM_001099270.4:c.*3582A>G (chr9-126884496-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

5 publications found

Variant links:

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]

ZBTB34 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
ZBTB34	NM_001099270.4 link	c.*3582A>G	3_prime_UTR_variant	Exon 2 of 2	ENST00000319119.5	NP_001092740.2	Q8NCN2
ZBTB34	NM_001395198.1 link	c.*3582A>G	3_prime_UTR_variant	Exon 3 of 3		NP_001382127.1
ZBTB34	XM_047423402.1 link	c.*3582A>G	3_prime_UTR_variant	Exon 3 of 3		XP_047279358.1
ZBTB34	XM_011518699.4 link	c.*3582A>G	3_prime_UTR_variant	Exon 2 of 2		XP_011517001.1	Q8NCN2A0A0C4DFQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB34	ENST00000319119.5 link	c.*3582A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001099270.4	ENSP00000317534.4		A0A0C4DFQ2
ZBTB34	ENST00000695642.1 link	c.*3582A>G		3_prime_UTR_variant	Exon 3 of 3			ENSP00000512077.1		A0A8Q3WKM1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17669

AN:

151232

Hom.:

1598

Cov.:

show subpopulations

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.:

AF XY:

0.156

AC XY:

1086

AN XY:

6968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.158

AC:

2292

AN:

14518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0930

AC:

AN:

Other (OTH)

AF:

0.0930

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.117

AC:

17672

AN:

151346

Hom.:

1594

Cov.:

AF XY:

0.124

AC XY:

9184

AN XY:

73894

show subpopulations

African (AFR)

AF:

0.0925

AC:

3822

AN:

41308

American (AMR)

AF:

0.0950

AC:

1442

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

231

AN:

3466

East Asian (EAS)

AF:

0.505

AC:

2605

AN:

5160

South Asian (SAS)

AF:

0.296

AC:

1424

AN:

4816

European-Finnish (FIN)

AF:

0.141

AC:

1458

AN:

10306

Middle Eastern (MID)

AF:

0.0931

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0943

AC:

6393

AN:

67810

Other (OTH)

AF:

0.0978

AC:

205

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

716

1432

2149

2865

3581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0932

Hom.:

1438

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

(source)

DANN

Benign

0.39

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over