Variant 11-7001232-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013249.4(ZNF214):c.451G>A(p.Gly151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,613,190 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 2 hom. )

Consequence

ZNF214
NM_013249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.318

Variant links:

Genes affected

ZNF214 (HGNC:13006): (zinc finger protein 214) This gene is expressed predominantly in the testis and encodes a zinc finger protein that contains an N-terminal kruppel-associated box A (KRABA) domain and twelve zinc finger domains. This gene is located within one of three regions on chromosome 11p15 associated with Beckwith-Wiedemann syndrome, called Beckwith-Wiedemann syndrome chromosome region-2 (BWSCR2), and is thought to play a role in the etiology of this disease. [provided by RefSeq, Aug 2017]

ZNF214 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=0.008826464).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF214	NM_013249.4 linkuse as main transcript	c.451G>A	p.Gly151Ser	missense_variant	3/3	ENST00000278314.5	NP_037381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF214	ENST00000278314.5 linkuse as main transcript	c.451G>A	p.Gly151Ser	missense_variant	3/3	1	NM_013249.4	ENSP00000278314	P1
ZNF214	ENST00000536068.5 linkuse as main transcript	c.451G>A	p.Gly151Ser	missense_variant	4/4	1		ENSP00000445373	P1

Frequencies

GnomAD3 genomes

AF:

0.000560

AC:

AN:

151852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.000972

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

251042

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000890

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000896

AC:

1309

AN:

1461220

Hom.:

Cov.:

AF XY:

0.000836

AC XY:

608

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000559

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000972

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000759

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000830

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 23, 2024

The c.451G>A (p.G151S) alteration is located in exon 3 (coding exon 2) of the ZNF214 gene. This alteration results from a G to A substitution at nucleotide position 451, causing the glycine (G) at amino acid position 151 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.5

DANN

Benign

0.39

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.49

.;T

M_CAP

Benign

0.00090

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.81

N;N

REVEL

Benign

0.019

Sift

Benign

0.40

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0010

B;B

Vest4

0.047

MVP

0.14

MPC

0.022

ClinPred

0.0025

GERP RS

0.77

Varity_R

0.043

gMVP

0.089

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