dbSNP rs1317401441: ZNF81:p.Lys200Gln (chrX-47915244-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007137.5(ZNF81):c.598A>C(p.Lys200Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,209,359 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06903291).

BS2

High Hemizygotes in GnomAdExome4 at 3 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF81	NM_007137.5 link	c.598A>C	p.Lys200Gln	missense_variant	Exon 5 of 5	ENST00000338637.13	NP_009068.2	P51508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF81	ENST00000338637.13 link	c.598A>C	p.Lys200Gln	missense_variant	Exon 5 of 5	3	NM_007137.5	ENSP00000341151.7	P51508
ZNF81	ENST00000376954.6 link	c.598A>C	p.Lys200Gln	missense_variant	Exon 6 of 6	5		ENSP00000366153.1	P51508
ZNF81	ENST00000376950.4 link	c.277+19304A>C		intron_variant	Intron 4 of 4	5		ENSP00000366149.4	B1AJV2

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112071

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000368

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000554

AC:

AN:

180600

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1097237

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362777

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26356

American (AMR)

AF:

0.00

AC:

AN:

35103

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19365

East Asian (EAS)

AF:

0.00

AC:

AN:

30187

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40508

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00000357

AC:

AN:

841504

Other (OTH)

AF:

0.00

AC:

AN:

46052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112122

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30924

American (AMR)

AF:

0.00

AC:

AN:

10563

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3587

South Asian (SAS)

AF:

0.000369

AC:

AN:

2710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53205

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2017

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.053

T;T

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.0068

.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.93

L;L

PhyloP100

1.5

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.070

Sift

Benign

0.040

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.019

B;B

Vest4

0.13

MutPred

0.23

Loss of methylation at K200 (P = 0.0219);Loss of methylation at K200 (P = 0.0219);

MVP

0.31

MPC

0.31

ClinPred

0.077

GERP RS

4.0

Varity_R

0.28

gMVP

0.089

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

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

rs1317401441

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over