rs17147793

Variant names:

• chrX-47914996-G-A
• rs17147793
• NM_007137.5:c.350G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-47914996-G-A
• chrX-47914996-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G117V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: ZNF81 NM_007137.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.673
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF81	NM_007137.5	c.350G>A	p.Gly117Asp	missense_variant	Exon 5 of 5	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000338637.13	c.350G>A	p.Gly117Asp	missense_variant	Exon 5 of 5	3	NM_007137.5	ENSP00000341151.7
ZNF81	ENST00000376954.6	c.350G>A	p.Gly117Asp	missense_variant	Exon 6 of 6	5		ENSP00000366153.1
ZNF81	ENST00000376950.4	c.277+19056G>A		intron_variant	Intron 4 of 4	5		ENSP00000366149.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000114 AC: 2 AN: 174889 AF XY: 0.0000163

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: 0.0000127

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

African (AFR) AF: 0.00 AC: 0 AN: 26256

American (AMR) AF: 0.00 AC: 0 AN: 34724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19230

East Asian (EAS) AF: 0.00 AC: 0 AN: 30126

South Asian (SAS) AF: 0.00 AC: 0 AN: 53318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4086

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839228

Other (OTH) AF: 0.00 AC: 0 AN: 45899

GnomAD4 genome Cov.: 23

Alfa AF: 0.0000223 Hom.: 109

ExAC AF: 0.0000331 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:2

Jun 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.350G>A (p.G117D) alteration is located in exon 5 (coding exon 4) of the ZNF81 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the glycine (G) at amino acid position 117 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Jul 01, 2014

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	0.080
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
PhyloP100		-0.67
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs17147793; hg19: chrX-47774395;