Variant X-153346831-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001367757.1(ZNF275):c.146C>T(p.Ala49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,192,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 11 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03372082).

BP6

Variant X-153346831-C-T is Benign according to our data. Variant chrX-153346831-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3335324.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.146C>T	p.Ala49Val	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.146C>T	p.Ala49Val	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.146C>T	p.Ala49Val	missense_variant	4/4		NM_001367757.1	ENSP00000496975.2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.-14C>T		5_prime_UTR_variant	3/3	1		ENSP00000359269.2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.146C>T	p.Ala49Val	missense_variant	4/5	2		ENSP00000359271.2	A6NFS0
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1358C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34056

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

163930

Hom.:

AF XY:

0.00

AC XY:

AN XY:

54288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000752

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000259

AC:

AN:

1080564

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

351924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000665

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000300

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34056

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000197

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0060

DANN

Benign

0.63

DEOGEN2

Benign

0.0058

T;T

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.20

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

1.0

.;N

REVEL

Benign

0.050

Sift

Benign

1.0

.;T

Sift4G

Benign

0.33

.;T

Polyphen

0.0

B;B

Vest4

0.025

MutPred

0.30

Loss of glycosylation at S48 (P = 0.1146);Loss of glycosylation at S48 (P = 0.1146);

MVP

0.47

MPC

0.34

ClinPred

0.039

GERP RS

-7.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.033

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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