X-47914996-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007137.5(ZNF81):​c.350G>A​(p.Gly117Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,251 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

ZNF81
NM_007137.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.673
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046092212).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF81NM_007137.5 linkuse as main transcriptc.350G>A p.Gly117Asp missense_variant 5/5 ENST00000338637.13 NP_009068.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF81ENST00000338637.13 linkuse as main transcriptc.350G>A p.Gly117Asp missense_variant 5/53 NM_007137.5 ENSP00000341151 P1
ZNF81ENST00000376954.6 linkuse as main transcriptc.350G>A p.Gly117Asp missense_variant 6/65 ENSP00000366153 P1
ZNF81ENST00000376950.4 linkuse as main transcriptc.277+19056G>A intron_variant 5 ENSP00000366149

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000114
AC:
2
AN:
174889
Hom.:
0
AF XY:
0.0000163
AC XY:
1
AN XY:
61521
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:
0.0000127
Gnomad OTH exome
AF:
0.000233
GnomAD4 exome
AF:
9.15e-7
AC:
1
AN:
1093251
Hom.:
0
Cov.:
30
AF XY:
0.00000278
AC XY:
1
AN XY:
359107
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:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Alfa
AF:
0.0000282
Hom.:
15
ExAC
AF:
0.0000331
AC:
4

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 submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 01, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.26
DANN
Benign
0.13
DEOGEN2
Benign
0.040
T;T
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.23
.;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.046
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.1
L;L
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.67
N;N
REVEL
Benign
0.032
Sift
Benign
0.58
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.0
B;B
Vest4
0.15
MutPred
0.32
Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP
0.28
MPC
0.20
ClinPred
0.019
T
GERP RS
1.3
Varity_R
0.072
gMVP
0.075

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

LitVar

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

Other links and lift over

dbSNP: rs17147793; hg19: chrX-47774395; API