Variant 19-24106617-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203282.4(ZNF254):c.227G>T(p.Arg76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ZNF254
NM_203282.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Variant links:

Genes affected

ZNF254 (HGNC:13047): (zinc finger protein 254) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

ZNF254 links:

ZNF254 (HGNC:):

ZNF254 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084748566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF254	NM_203282.4 linkuse as main transcript	c.227G>T	p.Arg76Leu	missense_variant	3/4	ENST00000357002.5	NP_975011.3	O75437-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF254	ENST00000357002.5 linkuse as main transcript	c.227G>T	p.Arg76Leu	missense_variant	3/4	1	NM_203282.4	ENSP00000349494.3		O75437-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250996

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 22, 2021

The c.227G>T (p.R76L) alteration is located in exon 3 (coding exon 3) of the ZNF254 gene. This alteration results from a G to T substitution at nucleotide position 227, causing the arginine (R) at amino acid position 76 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

.;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.27

T;D;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.085

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

.;.;.;L

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-6.5

.;.;D;D

REVEL

Benign

0.010

Sift

Uncertain

0.0020

.;.;D;D

Sift4G

Uncertain

0.034

D;D;D;D

Polyphen

0.19

.;.;.;B

Vest4

0.28

MutPred

0.41

.;.;Loss of disorder (P = 0.0426);Loss of disorder (P = 0.0426);

MVP

0.040

MPC

0.0015

ClinPred

0.21

GERP RS

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.043

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