rs11091216

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000334937.8(ZNF81):c.189C>T(p.Asp63Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,204,317 control chromosomes in the GnomAD database, including 357 homozygotes. There are 9,876 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 34 hom., 708 hem., cov: 22)

Exomes 𝑓: 0.026 ( 323 hom. 9168 hem. )

Consequence

ZNF81
ENST00000334937.8 synonymous

Scores

Splicing: ADA: 0.0004466

Clinical Significance

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

Conservation

PhyloP100: -0.0740

Publications

2 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=-0.87).

BP6

Variant X-47888133-C-T is Benign according to our data. Variant chrX-47888133-C-T is described in ClinVar as Benign. ClinVar VariationId is 95449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.074 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0197 (2184/110984) while in subpopulation NFE AF = 0.0284 (1505/52971). AF 95% confidence interval is 0.0272. There are 34 homozygotes in GnomAd4. There are 708 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF81	NM_007137.5 link	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000338637.13	NP_009068.2	P51508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF81	ENST00000334937.8 link	c.189C>T	p.Asp63Asp	synonymous_variant	Exon 4 of 4	1		ENSP00000334641.4	B1AJV1
ZNF81	ENST00000338637.13 link	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	3	NM_007137.5	ENSP00000341151.7	P51508
ZNF81	ENST00000376954.6 link	c.181+8C>T		splice_region_variant, intron_variant	Intron 4 of 5	5		ENSP00000366153.1	P51508
ZNF81	ENST00000376950.4 link	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	5		ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2183

AN:

110933

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00438

Gnomad AMR

AF:

0.00507

Gnomad ASJ

AF:

0.0148

Gnomad EAS

AF:

0.000564

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0732

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.0284

Gnomad OTH

AF:

0.0128

GnomAD2 exomes

AF:

0.0215

AC:

3664

AN:

170744

AF XY:

0.0212

show subpopulations

Gnomad AFR exome

AF:

0.00299

Gnomad AMR exome

AF:

0.00480

Gnomad ASJ exome

AF:

0.00835

Gnomad EAS exome

AF:

0.0000761

Gnomad FIN exome

AF:

0.0791

Gnomad NFE exome

AF:

0.0256

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0260

AC:

28381

AN:

1093333

Hom.:

323

Cov.:

AF XY:

0.0255

AC XY:

9168

AN XY:

359297

show subpopulations

African (AFR)

AF:

0.00300

AC:

AN:

26325

American (AMR)

AF:

0.00492

AC:

170

AN:

34518

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

198

AN:

19308

East Asian (EAS)

AF:

0.000133

AC:

AN:

30092

South Asian (SAS)

AF:

0.0157

AC:

842

AN:

53517

European-Finnish (FIN)

AF:

0.0739

AC:

2973

AN:

40234

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

4067

European-Non Finnish (NFE)

AF:

0.0275

AC:

23116

AN:

839370

Other (OTH)

AF:

0.0206

AC:

944

AN:

45902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

1021

2042

3064

4085

5106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.0197

AC:

2184

AN:

110984

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

708

AN XY:

33190

show subpopulations

African (AFR)

AF:

0.00318

AC:

AN:

30492

American (AMR)

AF:

0.00506

AC:

AN:

10475

Ashkenazi Jewish (ASJ)

AF:

0.0148

AC:

AN:

2644

East Asian (EAS)

AF:

0.000566

AC:

AN:

3536

South Asian (SAS)

AF:

0.0141

AC:

AN:

2619

European-Finnish (FIN)

AF:

0.0732

AC:

428

AN:

5846

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0284

AC:

1505

AN:

52971

Other (OTH)

AF:

0.0127

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

148

223

297

371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0263

Hom.:

219

Bravo

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 20, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.51

PhyloP100

-0.074

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00045

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over