Variant X-153347206-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367757.1(ZNF275):c.521T>C(p.Met174Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 1,207,994 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 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 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000091 ( 0 hom. 35 hem. )

Consequence

ZNF275
NM_001367757.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.671

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07367101).

BS2

High Hemizygotes in GnomAdExome4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF275	NM_001367757.1 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	4/4	ENST00000650114.2	NP_001354686.1
ZNF275	NM_001080485.4 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	4/5		NP_001073954.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF275	ENST00000650114.2 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	4/4		NM_001367757.1	ENSP00000496975	A2	Q9NSD4-1
ZNF275	ENST00000370249.3 linkuse as main transcript	c.362T>C	p.Met121Thr	missense_variant	3/3	1		ENSP00000359269	P2	Q9NSD4-2
ZNF275	ENST00000370251.3 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	4/5	2		ENSP00000359271
ZNF275	ENST00000647705.1 linkuse as main transcript	n.1733T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111153

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33401

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:

0.0000567

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000721

AC:

AN:

180217

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

66191

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000912

AC:

100

AN:

1096841

Hom.:

Cov.:

AF XY:

0.0000966

AC XY:

AN XY:

362371

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111153

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33401

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:

0.0000567

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000742

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

Apr 04, 2023

The c.521T>C (p.M174T) alteration is located in exon 4 (coding exon 3) of the ZNF275 gene. This alteration results from a T to C substitution at nucleotide position 521, causing the methionine (M) at amino acid position 174 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

0.14

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.090

DANN

Benign

0.33

DEOGEN2

Benign

0.020

.;T;T

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.074

Sift

Benign

0.17

T;.;T

Sift4G

Uncertain

0.057

T;.;T

Polyphen

0.0

.;B;B

Vest4

0.095

MVP

0.38

MPC

0.40

ClinPred

0.034

GERP RS

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.11

gMVP

0.26

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