Variant chrX-153347509-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367757.1(ZNF275):c.824G>A(p.Arg275Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000553 in 1,084,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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)

Exomes 𝑓: 0.0000055 ( 0 hom. 0 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0370

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1399158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.824G>A	p.Arg275Gln	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.824G>A	p.Arg275Gln	missense_variant	4/5		NP_001073954.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF275	ENST00000650114.2 linkuse as main transcript	c.824G>A	p.Arg275Gln	missense_variant	4/4		NM_001367757.1	ENSP00000496975	A2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.665G>A	p.Arg222Gln	missense_variant	3/3	1		ENSP00000359269	P2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.824G>A	p.Arg275Gln	missense_variant	4/5	2		ENSP00000359271
ZNF275	ENST00000647705.1 linkuse as main transcript	n.2036G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000181

AC:

AN:

165485

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54673

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000553

AC:

AN:

1084643

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

353321

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000257

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.824G>A (p.R275Q) 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 824, causing the arginine (R) at amino acid position 275 to be replaced by a glutamine (Q). 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

0.72

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.83

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

.;T;T

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.033

Sift

Benign

0.17

T;.;T

Sift4G

Benign

0.15

T;.;T

Polyphen

0.076, 0.13

.;B;B

Vest4

0.21

MutPred

0.27

.;Gain of methylation at K272 (P = 0.0464);Gain of methylation at K272 (P = 0.0464);

MVP

0.45

MPC

1.1

ClinPred

0.26

GERP RS

3.8

Varity_R

0.11

gMVP

0.10

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