Variant X-153347187-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.502G>A(p.Ala168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,208,083 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 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 0.000054 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000043 ( 0 hom. 22 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027667105).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.502G>A	p.Ala168Thr	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.502G>A	p.Ala168Thr	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.502G>A	p.Ala168Thr	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.343G>A	p.Ala115Thr	missense_variant	3/3	1		ENSP00000359269.2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.502G>A	p.Ala168Thr	missense_variant	4/5	2		ENSP00000359271.2	A6NFS0
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1714G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111546

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33726

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000750

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

179569

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

65707

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:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000995

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000429

AC:

AN:

1096482

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

362086

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000381

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111601

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

33791

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000751

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000908

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

Jun 21, 2021

The c.502G>A (p.A168T) 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 502, causing the alanine (A) at amino acid position 168 to be replaced by a threonine (T). 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

0.075

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.014

DANN

Benign

0.92

DEOGEN2

Benign

0.0077

.;T;T

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.16

N;.;N

REVEL

Benign

0.012

Sift

Uncertain

0.0070

D;.;D

Sift4G

Uncertain

0.0070

D;.;D

Polyphen

0.10, 0.0

.;B;B

Vest4

0.020

MVP

0.12

MPC

0.33

ClinPred

0.030

GERP RS

-7.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.095

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