X-153347229-G-A

Position:

chrX-153347229-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001367757.1(ZNF275):c.544G>A(p.Glu182Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,208,470 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000044 ( 0 hom. 22 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.17

Variant links:

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 links:

ZNF275 (HGNC:):

ZNF275 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.078021824).

BP6

Variant X-153347229-G-A is Benign according to our data. Variant chrX-153347229-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2591005.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.544G>A	p.Glu182Lys	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.544G>A	p.Glu182Lys	missense_variant	4/5		NP_001073954.3	A6NFS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF275	ENST00000650114.2 linkuse as main transcript	c.544G>A	p.Glu182Lys	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.385G>A	p.Glu129Lys	missense_variant	3/3	1		ENSP00000359269.2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.544G>A	p.Glu182Lys	missense_variant	4/5	2		ENSP00000359271.2	A6NFS0
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1756G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

111777

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33951

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000609

AC:

AN:

180622

Hom.:

AF XY:

0.0000602

AC XY:

AN XY:

66500

show subpopulations

Gnomad AFR exome

AF:

0.0000802

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1096693

Hom.:

Cov.:

AF XY:

0.0000607

AC XY:

AN XY:

362193

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000547

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000447

AC:

AN:

111777

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

33951

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.544G>A (p.E182K) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a G to A substitution at nucleotide position 544, causing the glutamic acid (E) at amino acid position 182 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZNF275: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

.;T;T

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.88

D;D;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

N;.;D

REVEL

Benign

0.022

Sift

Benign

0.36

T;.;T

Sift4G

Benign

0.18

T;.;T

Polyphen

0.017, 0.084

.;B;B

Vest4

0.076

MVP

0.50

MPC

0.49

ClinPred

0.049

GERP RS

1.8

Varity_R

0.13

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over