X-47915107-C-T

Position:

• chrX-47915107-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007137.5(ZNF81):​c.461C>T​(p.Thr154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZNF81 NM_007137.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0140

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0805991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF81	NM_007137.5	c.461C>T	p.Thr154Ile	missense_variant	5/5	ENST00000338637.13	NP_009068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF81	ENST00000338637.13	c.461C>T	p.Thr154Ile	missense_variant	5/5	3	NM_007137.5	ENSP00000341151	P1
ZNF81	ENST00000376954.6	c.461C>T	p.Thr154Ile	missense_variant	6/6	5		ENSP00000366153	P1
ZNF81	ENST00000376950.4	c.277+19167C>T		intron_variant		5		ENSP00000366149

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ZNF81: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.26
DEOGEN2	Benign	0.056	T;T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.16	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.57	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.011
Sift	Benign	0.092	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0070	B;B
Vest4		0.065
MutPred		0.38		Loss of ubiquitination at K159 (P = 0.0613);Loss of ubiquitination at K159 (P = 0.0613);
MVP		0.28
MPC		0.17
ClinPred		0.038	T
GERP RS		0.23
Varity_R		0.090
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47774506;