Variant chr19-21971395-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007153.3(ZNF208):c.3639A>T(p.Arg1213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00061 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF208
NM_007153.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.874

Variant links:

Genes affected

ZNF208 (HGNC:12999): (zinc finger protein 208) Zinc finger proteins (ZNFs), such as ZNF208, bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. A conserved protein motif, termed the Kruppel-associated box (KRAB) domain, mediates protein-protein interactions (Eichler et al., 1998 [PubMed 9724325]). See ZNF91 (MIM 603971) for further information on ZNFs.[supplied by OMIM, Aug 2009]

ZNF208 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016150415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF208	NM_007153.3 linkuse as main transcript	c.3639A>T	p.Arg1213Ser	missense_variant	4/4	ENST00000397126.9	NP_009084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF208	ENST00000397126.9 linkuse as main transcript	c.3639A>T	p.Arg1213Ser	missense_variant	4/4	3	NM_007153.3	ENSP00000380315	P1	O43345-1
ZNF208	ENST00000599916.5 linkuse as main transcript	c.305+3334A>T		intron_variant		1		ENSP00000469254
ZNF208	ENST00000601773.5 linkuse as main transcript	c.226+15821A>T		intron_variant		2		ENSP00000469887

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120580

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00108

Gnomad AMI

AF:

0.00160

Gnomad AMR

AF:

0.000401

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00158

Gnomad SAS

AF:

0.000842

Gnomad FIN

AF:

0.00134

Gnomad MID

AF:

0.00735

Gnomad NFE

AF:

0.000195

Gnomad OTH

AF:

0.00177

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

242708

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000225

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000973

AC:

AN:

1438854

Hom.:

Cov.:

129

AF XY:

0.00000838

AC XY:

AN XY:

716350

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000259

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000613

AC:

AN:

120648

Hom.:

Cov.:

AF XY:

0.000505

AC XY:

AN XY:

59438

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.000481

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00132

Gnomad4 SAS

AF:

0.000844

Gnomad4 FIN

AF:

0.00134

Gnomad4 NFE

AF:

0.000195

Gnomad4 OTH

AF:

0.00175

ExAC

AF:

0.0000331

AC:

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.3639A>T (p.R1213S) alteration is located in exon 4 (coding exon 4) of the ZNF208 gene. This alteration results from a A to T substitution at nucleotide position 3639, causing the arginine (R) at amino acid position 1213 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

0.22

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.4

DANN

Benign

0.24

DEOGEN2

Benign

0.0098

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.000080

LIST_S2

Benign

0.051

T;T

M_CAP

Benign

0.00061

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.99

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.54

.;N

REVEL

Benign

0.018

Sift

Benign

0.78

.;T

Sift4G

Benign

0.62

T;T

Vest4

0.17

MVP

0.055

MPC

0.0083

ClinPred

0.029

GERP RS

-6.4

Varity_R

0.077

gMVP

0.0054

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