Genetic Variant ZNF215:p.Phe237Cys (chr11-6943639-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_013250.4(ZNF215):c.710T>G(p.Phe237Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF215
NM_013250.4 missense, splice_region

Scores

Splicing: ADA: 0.00001294

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Variant links:

Genes affected

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:

LOC107984019 (HGNC:):

LOC107984019 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=0.06640604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF215	NM_013250.4 link	c.710T>G	p.Phe237Cys	missense_variant, splice_region_variant	Exon 6 of 7	ENST00000278319.10	NP_037382.2	Q9UL58-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF215	ENST00000278319.10 link	c.710T>G	p.Phe237Cys	missense_variant, splice_region_variant	Exon 6 of 7	1	NM_013250.4	ENSP00000278319.5		Q9UL58-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726204

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.5

DANN

Benign

0.34

DEOGEN2

Benign

0.0080

T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.34

.;T;T;.

M_CAP

Benign

0.0029

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

L;L;L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

0.050

N;.;N;N

REVEL

Benign

0.028

Sift

Benign

0.16

T;.;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.95

P;.;P;.

Vest4

0.35

MutPred

0.27

Loss of ubiquitination at K234 (P = 0.077);Loss of ubiquitination at K234 (P = 0.077);Loss of ubiquitination at K234 (P = 0.077);Loss of ubiquitination at K234 (P = 0.077);

MVP

0.14

MPC

0.0084

ClinPred

0.12

GERP RS

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.059

gMVP

0.035

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over