Variant X-153347169-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001367757.1(ZNF275):c.484A>G(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,200,850 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 135 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.00039 ( 0 hom. 134 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.28

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04951948).

BS2

High Hemizygotes in GnomAdExome4 at 134 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	4/4	ENST00000650114.2
ZNF275	NM_001080485.4 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF275	ENST00000650114.2 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	4/4		NM_001367757.1	A2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.325A>G	p.Arg109Gly	missense_variant	3/3	1		P2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.484A>G	p.Arg162Gly	missense_variant	4/5	2
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1696A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

111024

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33284

show subpopulations

Gnomad AFR

AF:

0.000131

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:

0.000246

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000128

AC:

AN:

179120

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

65334

show subpopulations

Gnomad AFR exome

AF:

0.0000811

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:

0.000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000389

AC:

424

AN:

1089826

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

134

AN XY:

356576

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

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:

0.000490

Gnomad4 OTH exome

AF:

0.000240

GnomAD4 genome

AF:

0.000153

AC:

AN:

111024

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33284

show subpopulations

Gnomad4 AFR

AF:

0.000131

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:

0.000246

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.000107

AC:

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

Jan 23, 2023

The c.484A>G (p.R162G) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a A to G substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a glycine (G). 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

Benign

0.082

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.091

DANN

Benign

0.83

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.37

N;.;N

REVEL

Benign

0.0060

Sift

Uncertain

0.0030

D;.;D

Sift4G

Uncertain

0.0030

D;.;D

Polyphen

0.0090, 0.023

.;B;B

Vest4

0.13

MVP

0.17

MPC

0.52

ClinPred

0.016

GERP RS

-3.4

Varity_R

0.073

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