11-7000132-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000278314.5(ZNF214):c.1551G>T(p.Gln517His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
ZNF214
ENST00000278314.5 missense
ENST00000278314.5 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 1.75
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]
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]
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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=0.23928112).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF214 | NM_013249.4 | c.1551G>T | p.Gln517His | 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 | c.1551G>T | p.Gln517His | missense_variant | 3/3 | 1 | NM_013249.4 | ENSP00000278314.4 | ||
ZNF214 | ENST00000536068.5 | c.1551G>T | p.Gln517His | missense_variant | 4/4 | 1 | ENSP00000445373.1 | |||
ZNF215 | ENST00000636606.1 | n.*216C>A | non_coding_transcript_exon_variant | 7/7 | 5 | ENSP00000490359.1 | ||||
ZNF215 | ENST00000636606.1 | n.*216C>A | 3_prime_UTR_variant | 7/7 | 5 | ENSP00000490359.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151910Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250634Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135458
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461346Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 726980
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151910Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74214
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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 | Feb 05, 2024 | The c.1551G>T (p.Q517H) alteration is located in exon 3 (coding exon 2) of the ZNF214 gene. This alteration results from a G to T substitution at nucleotide position 1551, causing the glutamine (Q) at amino acid position 517 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.1026);Loss of MoRF binding (P = 0.1026);
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at