Genetic Variant ZNF34:c.34-18T>C (chr8-144778182-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_001286769.2(ZNF34):c.34-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,604,922 control chromosomes in the GnomAD database, including 174,472 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 0.38 ( 13140 hom., cov: 32)

Exomes 𝑓: 0.46 ( 161332 hom. )

Consequence

ZNF34
NM_001286769.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.842

Publications

29 publications found

Variant links:

Genes affected

ZNF34 (HGNC:13098): (zinc finger protein 34) Predicted to enable DNA-binding transcription factor 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 cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF34 links:

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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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF34	NM_001286769.2 link	c.34-18T>C		intron_variant	Intron 3 of 5	ENST00000429371.7	NP_001273698.1	Q8IZ26A0A0C4DG42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF34	ENST00000429371.7 link	c.34-18T>C		intron_variant	Intron 3 of 5	1	NM_001286769.2	ENSP00000396894.2		A0A0C4DG42

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57789

AN:

151990

Hom.:

13143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.731

Gnomad SAS

AF:

0.564

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.383

GnomAD2 exomes

AF:

0.480

AC:

115068

AN:

239786

AF XY:

0.485

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.735

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.457

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.464

AC:

673818

AN:

1452814

Hom.:

161332

Cov.:

AF XY:

0.468

AC XY:

337900

AN XY:

722094

show subpopulations

African (AFR)

AF:

0.103

AC:

3447

AN:

33400

American (AMR)

AF:

0.528

AC:

23251

AN:

44048

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

10989

AN:

25174

East Asian (EAS)

AF:

0.733

AC:

29053

AN:

39660

South Asian (SAS)

AF:

0.558

AC:

47204

AN:

84650

European-Finnish (FIN)

AF:

0.468

AC:

24690

AN:

52782

Middle Eastern (MID)

AF:

0.313

AC:

1788

AN:

5704

European-Non Finnish (NFE)

AF:

0.457

AC:

506517

AN:

1107374

Other (OTH)

AF:

0.448

AC:

26879

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18440

36880

55321

73761

92201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15230

30460

45690

60920

76150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.380

AC:

57794

AN:

152108

Hom.:

13140

Cov.:

AF XY:

0.387

AC XY:

28741

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.122

AC:

5046

AN:

41524

American (AMR)

AF:

0.473

AC:

7230

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1501

AN:

3472

East Asian (EAS)

AF:

0.731

AC:

3777

AN:

5164

South Asian (SAS)

AF:

0.564

AC:

2719

AN:

4824

European-Finnish (FIN)

AF:

0.471

AC:

4980

AN:

10580

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31174

AN:

67950

Other (OTH)

AF:

0.384

AC:

810

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1688

3376

5063

6751

8439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.449

Hom.:

7806

Bravo

AF:

0.370

Asia WGS

AF:

0.602

AC:

2095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

8.2

(source)

DANN

Benign

0.64

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over