Variant X-47895893-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_007137.5(ZNF81):c.230A>G(p.Glu77Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,305 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35561717).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF81	NM_007137.5 linkuse as main transcript	c.230A>G	p.Glu77Gly	missense_variant	4/5	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF81	ENST00000338637.13 linkuse as main transcript	c.230A>G	p.Glu77Gly	missense_variant	4/5	3	NM_007137.5	ENSP00000341151	P1
ZNF81	ENST00000376954.6 linkuse as main transcript	c.230A>G	p.Glu77Gly	missense_variant	5/6	5		ENSP00000366153	P1
ZNF81	ENST00000376950.4 linkuse as main transcript	c.230A>G	p.Glu77Gly	missense_variant	4/5	5		ENSP00000366149

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000549

AC:

AN:

182145

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

66935

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097305

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362821

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.230A>G (p.E77G) alteration is located in exon 4 (coding exon 3) of the ZNF81 gene. This alteration results from a A to G substitution at nucleotide position 230, causing the glutamic acid (E) at amino acid position 77 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T;.

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.29

.;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.6

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.46

P;P;.

Vest4

0.29

MutPred

0.45

Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);Loss of solvent accessibility (P = 0.0098);

MVP

0.62

MPC

0.37

ClinPred

0.91

GERP RS

4.1

Varity_R

0.29

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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