Variant rs11091216 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007137.5(ZNF81):c.181+8C>T variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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
NM_007137.5 splice_region, intron

Scores

Splicing: ADA: 0.0004466

Clinical Significance

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

Conservation

PhyloP100: -0.0740

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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 id is 95449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47888133-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.181+8C>T		splice_region_variant, intron_variant		ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF81	ENST00000334937.8 linkuse as main transcript	c.189C>T	p.Asp63=	synonymous_variant	4/4	1		ENSP00000334641
ZNF81	ENST00000338637.13 linkuse as main transcript	c.181+8C>T		splice_region_variant, intron_variant		3	NM_007137.5	ENSP00000341151	P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.181+8C>T		splice_region_variant, intron_variant		5		ENSP00000366149
ZNF81	ENST00000376954.6 linkuse as main transcript	c.181+8C>T		splice_region_variant, intron_variant		5		ENSP00000366153	P1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2183

AN:

110933

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

708

AN XY:

33129

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

GnomAD3 exomes

AF:

0.0215

AC:

3664

AN:

170744

Hom.:

AF XY:

0.0212

AC XY:

1211

AN XY:

57246

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 SAS exome

AF:

0.0132

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

Gnomad4 AFR exome

AF:

0.00300

Gnomad4 AMR exome

AF:

0.00492

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0739

Gnomad4 NFE exome

AF:

0.0275

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0197

AC:

2184

AN:

110984

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

708

AN XY:

33190

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.00506

Gnomad4 ASJ

AF:

0.0148

Gnomad4 EAS

AF:

0.000566

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0732

Gnomad4 NFE

AF:

0.0284

Gnomad4 OTH

AF:

0.0127

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 20, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 01, 2013	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over