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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF81	NM_007137.5	MANE Select	c.350G>A	p.Gly117Asp	missense	Exon 5 of 5	NP_009068.2	P51508
	ZNF81	NM_001378152.1		c.350G>A	p.Gly117Asp	missense	Exon 6 of 6	NP_001365081.1	P51508
	ZNF81	NM_001378153.1		c.350G>A	p.Gly117Asp	missense	Exon 5 of 5	NP_001365082.1	P51508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF81	ENST00000338637.13	TSL:3 MANE Select	c.350G>A	p.Gly117Asp	missense	Exon 5 of 5	ENSP00000341151.7	P51508
	ZNF81	ENST00000376954.6	TSL:5	c.350G>A	p.Gly117Asp	missense	Exon 6 of 6	ENSP00000366153.1	P51508
	ZNF81	ENST00000853619.1		c.350G>A	p.Gly117Asp	missense	Exon 5 of 5	ENSP00000523678.1

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not specified (2)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.67
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.032
Sift	Benign	0.58	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.32		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;