rs145478020

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007137.5(ZNF81):c.18C>T(p.Asp6Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0099 in 1,207,438 control chromosomes in the GnomAD database, including 529 homozygotes. There are 3,971 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 80 hom., 527 hem., cov: 23)

Exomes 𝑓: 0.0095 ( 449 hom. 3444 hem. )

Consequence

ZNF81
NM_007137.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.680

Publications

6 publications found

Variant links:

Genes affected

ZNF81 (HGNC:13156): (zinc finger protein 81) This gene encodes a protein that likely functions as a transcription factor. The protein contains an N-terminal KRAB domain and several C2H2-type zinc finger motifs. Mutations in this gene cause an X-linked form of intellectual disability (MRX45). Microduplication of a region of chromosome X including this gene has also been associated with other forms of intellectual disability. [provided by RefSeq, Jul 2017]

ZNF81 Gene-Disease associations (from GenCC):

non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, X-linked 45
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
X-linked intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ZNF81 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant X-47846285-C-T is Benign according to our data. Variant chrX-47846285-C-T is described in ClinVar as Benign. ClinVar VariationId is 130853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF81	NM_007137.5 link	c.18C>T	p.Asp6Asp	synonymous_variant	Exon 2 of 5	ENST00000338637.13	NP_009068.2	P51508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000338637.13 link	c.18C>T	p.Asp6Asp	synonymous_variant	Exon 2 of 5	3	NM_007137.5	ENSP00000341151.7		P51508

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

1571

AN:

112152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0699

Gnomad ASJ

AF:

0.00265

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.0446

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000375

Gnomad OTH

AF:

0.0259

GnomAD2 exomes

AF:

0.0310

AC:

5397

AN:

173823

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.00261

Gnomad AMR exome

AF:

0.0939

Gnomad ASJ exome

AF:

0.00315

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0000670

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.00948

AC:

10382

AN:

1095232

Hom.:

449

Cov.:

AF XY:

0.00953

AC XY:

3444

AN XY:

361240

show subpopulations

African (AFR)

AF:

0.00167

AC:

AN:

26371

American (AMR)

AF:

0.0929

AC:

3241

AN:

34882

Ashkenazi Jewish (ASJ)

AF:

0.00238

AC:

AN:

19335

East Asian (EAS)

AF:

0.140

AC:

4230

AN:

30135

South Asian (SAS)

AF:

0.0311

AC:

1660

AN:

53381

European-Finnish (FIN)

AF:

0.0000248

AC:

AN:

40255

Middle Eastern (MID)

AF:

0.00141

AC:

AN:

3536

European-Non Finnish (NFE)

AF:

0.000307

AC:

258

AN:

841366

Other (OTH)

AF:

0.0195

AC:

897

AN:

45971

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

384

768

1153

1537

1921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.0140

AC:

1567

AN:

112206

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

527

AN XY:

34372

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

30883

American (AMR)

AF:

0.0701

AC:

743

AN:

10602

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

2646

East Asian (EAS)

AF:

0.163

AC:

575

AN:

3532

South Asian (SAS)

AF:

0.0436

AC:

118

AN:

2707

European-Finnish (FIN)

AF:

0.000163

AC:

AN:

6153

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000376

AC:

AN:

53256

Other (OTH)

AF:

0.0262

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00463

Hom.:

Bravo

AF:

0.0200

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 07, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.7

(source)

DANN

Benign

0.86

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over