X-153347261-G-T

Position:

• chrX-153347261-G-T

Variant summary

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

The NM_001367757.1(ZNF275):​c.576G>T​(p.Lys192Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: ZNF275 NM_001367757.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.712

Genes affected

ZNF275 (HGNC:13069): (zinc finger protein 275) This gene encodes a zinc finger protein that appears to be conserved in eutheria. Its function has not yet been established. [provided by RefSeq, Jul 2010]

ZNF275 (HGNC:):

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=0.14876217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1	c.576G>T	p.Lys192Asn	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4	c.576G>T	p.Lys192Asn	missense_variant	4/5		NP_001073954.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF275	ENST00000650114.2	c.576G>T	p.Lys192Asn	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2
ZNF275	ENST00000370249.3	c.417G>T	p.Lys139Asn	missense_variant	3/3	1		ENSP00000359269.2
ZNF275	ENST00000370251.3	c.576G>T	p.Lys192Asn	missense_variant	4/5	2		ENSP00000359271.2
ZNF275	ENST00000647705.1	n.1788G>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.576G>T (p.K192N) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a G to T substitution at nucleotide position 576, causing the lysine (K) at amino acid position 192 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	.;T;T
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.070	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.065
Sift	Benign	0.19	T;.;T
Sift4G	Benign	0.17	T;.;T
Polyphen		0.68	.;P;P
Vest4		0.049
MutPred		0.34		.;Loss of ubiquitination at K192 (P = 0.0155);Loss of ubiquitination at K192 (P = 0.0155);
MVP		0.62
MPC		1.2
ClinPred		0.67	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.17

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-152612719;