dbSNP rs200074368: ZNF81:p.Lys170Arg (chrX-47915155-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007137.5(ZNF81):c.509A>G(p.Lys170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,198,016 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., 22 hem., cov: 23)

Exomes 𝑓: 0.000060 ( 0 hom. 20 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0940

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047689974).

BS2

High Hemizygotes in GnomAd4 at 22 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007137.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF81	NM_007137.5	MANE Select	c.509A>G	p.Lys170Arg	missense	Exon 5 of 5	NP_009068.2	P51508
ZNF81	NM_001378152.1		c.509A>G	p.Lys170Arg	missense	Exon 6 of 6	NP_001365081.1	P51508
ZNF81	NM_001378153.1		c.509A>G	p.Lys170Arg	missense	Exon 5 of 5	NP_001365082.1	P51508

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF81	ENST00000338637.13	TSL:3 MANE Select	c.509A>G	p.Lys170Arg	missense	Exon 5 of 5	ENSP00000341151.7	P51508
ZNF81	ENST00000376954.6	TSL:5	c.509A>G	p.Lys170Arg	missense	Exon 6 of 6	ENSP00000366153.1	P51508
ZNF81	ENST00000853619.1		c.509A>G	p.Lys170Arg	missense	Exon 5 of 5	ENSP00000523678.1

Frequencies

GnomAD3 genomes

AF:

0.000634

AC:

AN:

111955

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000196

AC:

AN:

167969

AF XY:

0.000227

show subpopulations

Gnomad AFR exome

AF:

0.00257

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000599

AC:

AN:

1086013

Hom.:

Cov.:

AF XY:

0.0000563

AC XY:

AN XY:

355003

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

25678

American (AMR)

AF:

0.0000303

AC:

AN:

33022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18834

East Asian (EAS)

AF:

0.00

AC:

AN:

30053

South Asian (SAS)

AF:

0.00

AC:

AN:

51683

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40167

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837051

Other (OTH)

AF:

0.000132

AC:

AN:

45479

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000652

AC:

AN:

112003

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

34185

show subpopulations

African (AFR)

AF:

0.00223

AC:

AN:

30899

American (AMR)

AF:

0.000285

AC:

AN:

10514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.00

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53186

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000303

Hom.:

Bravo

AF:

0.000638

ESP6500AA

AF:

0.00230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000224

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.055

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.28

M_CAP

Benign

0.00097

MetaRNN

Benign

0.0048

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

0.094

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.040

Sift

Benign

0.10

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.084

MVP

0.17

MPC

0.12

ClinPred

0.013

GERP RS

1.8

Varity_R

0.050

gMVP

0.073

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over