Genetic Variant ZNF135:p.Tyr242Tyr (chr19-58067210-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001289401.2(ZNF135):c.726C>T(p.Tyr242Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,613,856 control chromosomes in the GnomAD database, including 127,026 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 ( 11230 hom., cov: 32)

Exomes 𝑓: 0.40 ( 115796 hom. )

Consequence

ZNF135
NM_001289401.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

20 publications found

Variant links:

Genes affected

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF135 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.003).

BP7

Synonymous conserved (PhyloP=-1.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF135	NM_001289401.2 link	c.726C>T	p.Tyr242Tyr	synonymous_variant	Exon 5 of 5	ENST00000313434.10	NP_001276330.1	P52742-1Q8N9M3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF135	ENST00000313434.10 link	c.726C>T	p.Tyr242Tyr	synonymous_variant	Exon 5 of 5	1	NM_001289401.2	ENSP00000321406.5		P52742-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58060

AN:

151856

Hom.:

11218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.401

GnomAD2 exomes

AF:

0.400

AC:

100627

AN:

251368

AF XY:

0.401

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.395

AC:

577484

AN:

1461882

Hom.:

115796

Cov.:

AF XY:

0.396

AC XY:

288093

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.352

AC:

11794

AN:

33480

American (AMR)

AF:

0.510

AC:

22789

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

11831

AN:

26136

East Asian (EAS)

AF:

0.276

AC:

10941

AN:

39700

South Asian (SAS)

AF:

0.423

AC:

36493

AN:

86258

European-Finnish (FIN)

AF:

0.352

AC:

18802

AN:

53414

Middle Eastern (MID)

AF:

0.431

AC:

2488

AN:

5768

European-Non Finnish (NFE)

AF:

0.394

AC:

438427

AN:

1112006

Other (OTH)

AF:

0.396

AC:

23919

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

26654

53309

79963

106618

133272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13628

27256

40884

54512

68140

<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:

0.382

AC:

58108

AN:

151974

Hom.:

11230

Cov.:

AF XY:

0.380

AC XY:

28197

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.354

AC:

14658

AN:

41422

American (AMR)

AF:

0.441

AC:

6739

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1606

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1169

AN:

5144

South Asian (SAS)

AF:

0.410

AC:

1976

AN:

4816

European-Finnish (FIN)

AF:

0.352

AC:

3727

AN:

10576

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27018

AN:

67960

Other (OTH)

AF:

0.396

AC:

834

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1859

3718

5577

7436

9295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.405

Hom.:

24865

Bravo

AF:

0.387

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

EpiCase

AF:

0.413

EpiControl

AF:

0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.82

PhyloP100

-1.6

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over