Variant chr11-7000875-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013249.4(ZNF214):c.808A>G(p.Ile270Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF214
NM_013249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0910

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:

ZNF215 (HGNC:13007): (zinc finger protein 215) This gene is imprinted in a tissue-specific manner with preferential expression in the testis, and encodes a zinc finger protein that belongs to a family of zinc finger transcription factors. The encoded protein contains an N-terminal SRE-ZBP, Ctfin51, AW-1, and Number 18 (SCAN) domain, a kruppel-associated box A (KRABA) domain, and four C-terminal 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]

ZNF215 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044142038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF214	NM_013249.4 link	c.808A>G	p.Ile270Val	missense_variant	3/3	ENST00000278314.5	NP_037381.2	Q9UL59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF214	ENST00000278314.5 link	c.808A>G	p.Ile270Val	missense_variant	3/3	1	NM_013249.4	ENSP00000278314.4	Q9UL59
ZNF214	ENST00000536068.5 link	c.808A>G	p.Ile270Val	missense_variant	4/4	1		ENSP00000445373.1	Q9UL59
ZNF215	ENST00000636606.1 link	n.*959T>C		non_coding_transcript_exon_variant	7/7	5		ENSP00000490359.1	A0A1B0GV37
ZNF215	ENST00000636606.1 link	n.*959T>C		3_prime_UTR_variant	7/7	5		ENSP00000490359.1	A0A1B0GV37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249512

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134852

show subpopulations

Gnomad AFR exome

AF:

0.0000617

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461068

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

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

Dec 09, 2024

The c.808A>G (p.I270V) alteration is located in exon 3 (coding exon 2) of the ZNF214 gene. This alteration results from a A to G substitution at nucleotide position 808, causing the isoleucine (I) at amino acid position 270 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.8

DANN

Benign

0.48

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.92

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.26

.;T

M_CAP

Benign

0.00081

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.26

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.030

Sift

Benign

0.50

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0

B;B

Vest4

0.043

MutPred

0.56

Gain of ubiquitination at K273 (P = 0.0585);Gain of ubiquitination at K273 (P = 0.0585);

MVP

0.22

MPC

0.021

ClinPred

0.069

GERP RS

0.10

Varity_R

0.024

gMVP

0.017

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