Variant X-153347503-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367757.1(ZNF275):c.818C>G(p.Ser273Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,198,956 control chromosomes in the GnomAD database, including 1 homozygotes. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.00014 ( 1 hom. 45 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.207

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21485418).

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.818C>G	p.Ser273Cys	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.818C>G	p.Ser273Cys	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.818C>G	p.Ser273Cys	missense_variant	4/4		NM_001367757.1	ENSP00000496975	A2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.659C>G	p.Ser220Cys	missense_variant	3/3	1		ENSP00000359269	P2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.818C>G	p.Ser273Cys	missense_variant	4/5	2		ENSP00000359271
ZNF275	ENST00000647705.1 linkuse as main transcript	n.2030C>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000354

AC:

AN:

113120

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

35282

show subpopulations

Gnomad AFR

AF:

0.0000321

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000179

AC:

AN:

167414

Hom.:

AF XY:

0.0000179

AC XY:

AN XY:

55908

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000397

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

156

AN:

1085836

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

353986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000539

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.0000439

GnomAD4 genome

AF:

0.0000354

AC:

AN:

113120

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

35282

show subpopulations

Gnomad4 AFR

AF:

0.0000321

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:

0.0000563

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000825

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, 2024

The c.818C>G (p.S273C) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a C to G substitution at nucleotide position 818, causing the serine (S) at amino acid position 273 to be replaced by a cysteine (C). 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

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

.;T;T

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

T;T;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.99

.;L;.

MutationTaster

Benign

0.54

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

N;.;N

REVEL

Benign

0.10

Sift

Uncertain

0.0080

D;.;D

Sift4G

Pathogenic

0.0010

D;.;D

Polyphen

0.99, 1.0

.;D;D

Vest4

0.32

MVP

0.56

MPC

1.1

ClinPred

0.39

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.23

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