ENST00000334937.8:c.189C>T

Variant names:

• chrX-47888133-C-T
• rs11091216
• ENST00000334937.8:c.189C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000334937.8(ZNF81):​c.189C>T​(p.Asp63Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,204,317 control chromosomes in the GnomAD database, including 357 homozygotes. There are 9,876 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (34 hom., 708 hem., cov: 22)
  • Exomes 𝑓: 0.026 (323 hom. 9168 hem.)
• Consequence: ZNF81 ENST00000334937.8 synonymous
• Scores: Splicing: ADA: 0.0004466
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0740

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-47888133-C-T is Benign according to our data. Variant chrX-47888133-C-T is described in ClinVar as [Benign]. Clinvar id is 95449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47888133-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.074 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (2184/110984) while in subpopulation NFE AF= 0.0284 (1505/52971). AF 95% confidence interval is 0.0272. There are 34 homozygotes in gnomad4. There are 708 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF81	NM_007137.5	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000334937.8	c.189C>T	p.Asp63Asp	synonymous_variant	Exon 4 of 4	1		ENSP00000334641.4
ZNF81	ENST00000338637.13	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	3	NM_007137.5	ENSP00000341151.7
ZNF81	ENST00000376954.6	c.181+8C>T		splice_region_variant, intron_variant	Intron 4 of 5	5		ENSP00000366153.1
ZNF81	ENST00000376950.4	c.181+8C>T		splice_region_variant, intron_variant	Intron 3 of 4	5		ENSP00000366149.4

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2183 AN: 110933 Hom.: 34 Cov.: 22 AF XY: 0.0214 AC XY: 708 AN XY: 33129

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00438

Gnomad AMR AF: 0.00507

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.000564

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0128

GnomAD3 exomes AF: 0.0215 AC: 3664 AN: 170744 Hom.: 64 AF XY: 0.0212 AC XY: 1211 AN XY: 57246

Gnomad AFR exome AF: 0.00299

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.00835

Gnomad EAS exome AF: 0.0000761

Gnomad SAS exome AF: 0.0132

Gnomad FIN exome AF: 0.0791

Gnomad NFE exome AF: 0.0256

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0260 AC: 28381 AN: 1093333 Hom.: 323 Cov.: 31 AF XY: 0.0255 AC XY: 9168 AN XY: 359297

Gnomad4 AFR exome AF: 0.00300

Gnomad4 AMR exome AF: 0.00492

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.000133

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0739

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0197 AC: 2184 AN: 110984 Hom.: 34 Cov.: 22 AF XY: 0.0213 AC XY: 708 AN XY: 33190

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00506

Gnomad4 ASJ AF: 0.0148

Gnomad4 EAS AF: 0.000566

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0127

Alfa AF: 0.0263 Hom.: 219

Bravo AF: 0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 20, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 01, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.034
SpliceAI score (max)		0.030		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: rs11091216; hg19: chrX-47747532;