Variant 19-43962805-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000587682.6(ZNF221):c.79A>C(p.Lys27Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF221
ENST00000587682.6 missense, splice_region

Scores

Splicing: ADA: 0.00009952

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Variant links:

Genes affected

ZNF221 (HGNC:13014): (zinc finger protein 221) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF221 links:

ZNF221 (HGNC:):

ZNF221 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=0.06947249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF221	NM_001297588.2 linkuse as main transcript	c.79A>C	p.Lys27Gln	missense_variant, splice_region_variant	2/5	ENST00000587682.6	NP_001284517.1	Q9UK13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF221	ENST00000587682.6 linkuse as main transcript	c.79A>C	p.Lys27Gln	missense_variant, splice_region_variant	2/5	1	NM_001297588.2	ENSP00000467367.1		Q9UK13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250870

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

6.84e-7

AC:

AN:

1461110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

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.79A>C (p.K27Q) alteration is located in exon 3 (coding exon 1) of the ZNF221 gene. This alteration results from a A to C substitution at nucleotide position 79, causing the lysine (K) at amino acid position 27 to be replaced by a glutamine (Q). 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

0.088

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.0040

.;T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.048

.;.;.;.;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.069

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

.;.;N;.;.

REVEL

Benign

0.062

Sift

Benign

0.56

.;.;T;.;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.027

.;B;B;B;B

Vest4

0.33, 0.32, 0.33, 0.33

MutPred

0.49

Loss of methylation at K27 (P = 0.0028);Loss of methylation at K27 (P = 0.0028);Loss of methylation at K27 (P = 0.0028);Loss of methylation at K27 (P = 0.0028);Loss of methylation at K27 (P = 0.0028);

MVP

0.092

MPC

0.025

ClinPred

0.046

GERP RS

2.0

Varity_R

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0060

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