Variant 19-21971387-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_007153.3(ZNF208):c.3647A>G(p.Lys1216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000027 ( 0 hom. )

Consequence

ZNF208
NM_007153.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.168

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:

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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=0.051668078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF208	NM_007153.3 linkuse as main transcript	c.3647A>G	p.Lys1216Arg	missense_variant	4/4	ENST00000397126.9	NP_009084.2	O43345-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF208	ENST00000397126.9 linkuse as main transcript	c.3647A>G	p.Lys1216Arg	missense_variant	4/4	3	NM_007153.3	ENSP00000380315.3	O43345-1
ZNF208	ENST00000599916.5 linkuse as main transcript	c.305+3342A>G		intron_variant		1		ENSP00000469254.1	M0QXL7
ZNF208	ENST00000601773.5 linkuse as main transcript	c.226+15829A>G		intron_variant		2		ENSP00000469887.1	M0QYK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458302

Hom.:

Cov.:

125

AF XY:

0.00000276

AC XY:

AN XY:

725588

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

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

Dec 21, 2023

The c.3647A>G (p.K1216R) alteration is located in exon 4 (coding exon 4) of the ZNF208 gene. This alteration results from a A to G substitution at nucleotide position 3647, causing the lysine (K) at amino acid position 1216 to be replaced by an arginine (R). 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

0.085

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0014

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.00074

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.52

.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.33

.;N

REVEL

Benign

0.015

Sift

Benign

0.67

.;T

Sift4G

Benign

0.17

T;T

Vest4

0.13

MVP

0.040

MPC

0.015

ClinPred

0.15

GERP RS

1.6

Varity_R

0.030

gMVP

0.0031

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over