Genetic Variant ZNF84:c.143-63A>T (chr12-133048690-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001289971.2(ZNF84):c.143-63A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,296,676 control chromosomes in the GnomAD database, including 123,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16879 hom., cov: 32)

Exomes 𝑓: 0.43 ( 106166 hom. )

Consequence

ZNF84
NM_001289971.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.858

Publications

2 publications found

Variant links:

Genes affected

ZNF84 (HGNC:13159): (zinc finger protein 84) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF84 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 12-133048690-A-T is Benign according to our data. Variant chr12-133048690-A-T is described in ClinVar as Benign. ClinVar VariationId is 982074.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF84	NM_001289971.2	MANE Select	c.143-63A>T	intron	N/A	NP_001276900.1	P51523
ZNF84	NM_001127372.3		c.143-63A>T	intron	N/A	NP_001120844.1	P51523
ZNF84	NM_001289972.2		c.143-63A>T	intron	N/A	NP_001276901.1	P51523

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF84	ENST00000539354.6	TSL:1 MANE Select	c.143-63A>T	intron	N/A	ENSP00000445549.1	P51523
ZNF84	ENST00000327668.11	TSL:1	c.143-63A>T	intron	N/A	ENSP00000331465.7	P51523
ZNF84	ENST00000392319.6	TSL:1	c.143-63A>T	intron	N/A	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69907

AN:

151844

Hom.:

16869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.429

Gnomad OTH

AF:

0.404

GnomAD4 exome

AF:

0.426

AC:

487268

AN:

1144716

Hom.:

106166

Cov.:

AF XY:

0.427

AC XY:

247702

AN XY:

580166

show subpopulations

African (AFR)

AF:

0.603

AC:

16138

AN:

26742

American (AMR)

AF:

0.306

AC:

11805

AN:

38564

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

8459

AN:

23010

East Asian (EAS)

AF:

0.223

AC:

8213

AN:

36818

South Asian (SAS)

AF:

0.458

AC:

34844

AN:

76086

European-Finnish (FIN)

AF:

0.425

AC:

21283

AN:

50024

Middle Eastern (MID)

AF:

0.368

AC:

1886

AN:

5128

European-Non Finnish (NFE)

AF:

0.434

AC:

364069

AN:

839260

Other (OTH)

AF:

0.419

AC:

20571

AN:

49084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13010

26020

39029

52039

65049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9992

19984

29976

39968

49960

<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:

0.460

AC:

69944

AN:

151960

Hom.:

16879

Cov.:

AF XY:

0.455

AC XY:

33823

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.600

AC:

24849

AN:

41420

American (AMR)

AF:

0.351

AC:

5361

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1282

AN:

3470

East Asian (EAS)

AF:

0.223

AC:

1151

AN:

5164

South Asian (SAS)

AF:

0.452

AC:

2172

AN:

4806

European-Finnish (FIN)

AF:

0.437

AC:

4615

AN:

10556

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.429

AC:

29168

AN:

67950

Other (OTH)

AF:

0.401

AC:

847

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1872

3743

5615

7486

9358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.249

Hom.:

423

Bravo

AF:

0.454

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.1

(source)

DANN

Benign

0.81

PhyloP100

-0.86

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over