X-47895879-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_007137.5(ZNF81):c.216G>A(p.Lys72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,209,479 control chromosomes in the GnomAD database, including 1 homozygotes. There are 121 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00021 (1 hom. 116 hem.)
• Consequence: ZNF81 NM_007137.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.600

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-47895879-G-A is Benign according to our data. Variant chrX-47895879-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.6 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF81	NM_007137.5	c.216G>A	p.Lys72=	synonymous_variant	4/5	ENST00000338637.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF81	ENST00000338637.13	c.216G>A	p.Lys72=	synonymous_variant	4/5	3	NM_007137.5	P1
ZNF81	ENST00000376954.6	c.216G>A	p.Lys72=	synonymous_variant	5/6	5		P1
ZNF81	ENST00000376950.4	c.216G>A	p.Lys72=	synonymous_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.000143 AC: 16 AN: 112157 Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 5 AN XY: 34325

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000944

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00184

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000346 AC: 63 AN: 181904 Hom.: 1 AF XY: 0.000614 AC XY: 41 AN XY: 66740

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: 0.00265

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.000224

GnomAD4 exome AF: 0.000214 AC: 235 AN: 1097268 Hom.: 1 Cov.: 30 AF XY: 0.000320 AC XY: 116 AN XY: 362808

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: 0.00239

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000986

Gnomad4 OTH exome AF: 0.000369

GnomAD4 genome AF: 0.000143 AC: 16 AN: 112211 Hom.: 0 Cov.: 23 AF XY: 0.000145 AC XY: 5 AN XY: 34389

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000943

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00184

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000347 Hom.: 3

Bravo AF: 0.000121

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

ZNF81: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	6.7
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs782802456; hg19: chrX-47755278;