Variant X-153346957-G-A 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.272G>A(p.Ser91Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000909 in 1,209,881 control chromosomes in the GnomAD database, including 1 homozygotes. There are 31 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 0.000063 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000094 ( 1 hom. 30 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0820

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=0.059529036).

BS2

High Hemizygotes in GnomAdExome4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 link	c.272G>A	p.Ser91Asn	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 link	c.272G>A	p.Ser91Asn	missense_variant	4/5		NP_001073954.3	A6NFS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF275	ENST00000650114.2 link	c.272G>A	p.Ser91Asn	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2	Q9NSD4-1
ZNF275	ENST00000370249.3 link	c.113G>A	p.Ser38Asn	missense_variant	3/3	1		ENSP00000359269.2	Q9NSD4-2
ZNF275	ENST00000370251.3 link	c.272G>A	p.Ser91Asn	missense_variant	4/5	2		ENSP00000359271.2	A6NFS0
ZNF275	ENST00000647705.1 link	n.1484G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

111765

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33917

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000826

AC:

AN:

181607

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

67571

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000738

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000938

AC:

103

AN:

1098116

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

363544

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.0000626

AC:

AN:

111765

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33917

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000153

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

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

May 08, 2023

The c.272G>A (p.S91N) 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 272, causing the serine (S) at amino acid position 91 to be replaced by an asparagine (N). 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

0.098

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-1.1

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.011

.;T;T

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

.;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.35

N;.;N

REVEL

Benign

0.013

Sift

Benign

0.25

T;.;T

Sift4G

Benign

0.27

T;.;T

Polyphen

0.0010

.;B;B

Vest4

0.015

MVP

0.32

MPC

0.33

ClinPred

0.013

GERP RS

2.3

Varity_R

0.080

gMVP

0.024

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