Genetic Variant NM_007137.5:c.12C>T (chrX-47846279-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_007137.5(ZNF81):c.12C>T(p.Asn4Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,207,582 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000011 ( 0 hom. 5 hem. )

Consequence

ZNF81
NM_007137.5 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.392

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=-0.392 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 Unknown,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF81	NM_007137.5 link	c.12C>T	p.Asn4Asn	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.12C>T	p.Asn4Asn	synonymous_variant	Exon 2 of 5	3	NM_007137.5	ENSP00000341151.7		P51508

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112209

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000575

AC:

AN:

174001

AF XY:

0.0000164

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:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1095320

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361312

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26366

American (AMR)

AF:

0.00

AC:

AN:

34998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19330

East Asian (EAS)

AF:

0.00

AC:

AN:

30165

South Asian (SAS)

AF:

0.00

AC:

AN:

53362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3485

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

841387

Other (OTH)

AF:

0.00

AC:

AN:

45961

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34420

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30886

American (AMR)

AF:

0.00

AC:

AN:

10612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00

AC:

AN:

2725

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6149

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53239

Other (OTH)

AF:

0.00

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

Jun 29, 2015

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.89

PhyloP100

-0.39

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

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NM_007137.5:c.12C>T

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