Variant X-153347572-C-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.887C>A(p.Pro296His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000337 in 1,188,251 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.000018 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.314

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 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=0.073877186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.887C>A	p.Pro296His	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.887C>A	p.Pro296His	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.887C>A	p.Pro296His	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.728C>A	p.Pro243His	missense_variant	3/3	1		ENSP00000359269.2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.887C>A	p.Pro296His	missense_variant	4/5	2		ENSP00000359271.2	A6NFS0
ZNF275	ENST00000647705.1 linkuse as main transcript	n.2099C>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112357

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34605

show subpopulations

Gnomad AFR

AF:

0.0000647

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000659

AC:

AN:

151832

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

45270

show subpopulations

Gnomad AFR exome

AF:

0.0000879

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000186

AC:

AN:

1075894

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

348026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000773

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112357

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34605

show subpopulations

Gnomad4 AFR

AF:

0.0000647

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Dec 14, 2023

The c.887C>A (p.P296H) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a C to A substitution at nucleotide position 887, causing the proline (P) at amino acid position 296 to be replaced by a histidine (H). 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

0.33

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.7

DANN

Benign

0.96

DEOGEN2

Benign

0.0046

.;T;T

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

1.4

N;.;N

REVEL

Benign

0.014

Sift

Benign

0.12

T;.;T

Sift4G

Benign

0.090

T;.;T

Polyphen

0.19, 0.68

.;B;P

Vest4

0.16

MutPred

0.30

.;Gain of MoRF binding (P = 0.0505);Gain of MoRF binding (P = 0.0505);

MVP

0.48

MPC

1.0

ClinPred

0.023

GERP RS

-1.8

Varity_R

0.10

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

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