Variant chrX-153346830-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.145G>A(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,191,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A49V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 11 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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=0.024740845).

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	4/4	ENST00000650114.2
ZNF275	NM_001080485.4 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF275	ENST00000650114.2 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	4/4		NM_001367757.1	A2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.-15G>A		5_prime_UTR_variant	3/3	1		P2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	4/5	2
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1357G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111784

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33968

show subpopulations

Gnomad AFR

AF:

0.000586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000471

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:

0.0000733

AC:

AN:

163641

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

54085

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000752

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.000250

GnomAD4 exome

AF:

0.0000333

AC:

AN:

1080120

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

351632

show subpopulations

Gnomad4 AFR exome

AF:

0.000655

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000999

Gnomad4 SAS exome

AF:

0.0000196

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000442

GnomAD4 genome

AF:

0.000215

AC:

AN:

111836

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

AN XY:

34030

show subpopulations

Gnomad4 AFR

AF:

0.000617

Gnomad4 AMR

AF:

0.000470

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

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000289

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000497

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

Sep 19, 2022

The c.145G>A (p.A49T) 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 145, causing the alanine (A) at amino acid position 49 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

0.069

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.1

CADD

Benign

6.1

DANN

Benign

0.52

DEOGEN2

Benign

0.0079

T;T

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

Polyphen

0.0030

B;B

Vest4

0.036

MVP

0.55

MPC

0.36

ClinPred

0.0036

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.035

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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