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GeneBe

19-21971384-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007153.3(ZNF208):​c.3650A>T​(p.Lys1217Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNF208
NM_007153.3 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07211983).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF208NM_007153.3 linkuse as main transcriptc.3650A>T p.Lys1217Ile missense_variant 4/4 ENST00000397126.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF208ENST00000397126.9 linkuse as main transcriptc.3650A>T p.Lys1217Ile missense_variant 4/43 NM_007153.3 P1O43345-1
ZNF208ENST00000599916.5 linkuse as main transcriptc.305+3345A>T intron_variant 1
ZNF208ENST00000601773.5 linkuse as main transcriptc.226+15832A>T intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
3
AN:
144614
Hom.:
0
Cov.:
32
FAILED QC
Gnomad AFR
AF:
0.0000257
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000303
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000164
AC:
4
AN:
243350
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132642
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000507
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000213
AC:
31
AN:
1457086
Hom.:
0
Cov.:
126
AF XY:
0.0000234
AC XY:
17
AN XY:
724984
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000592
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000207
AC:
3
AN:
144720
Hom.:
0
Cov.:
32
AF XY:
0.0000142
AC XY:
1
AN XY:
70646
show subpopulations
Gnomad4 AFR
AF:
0.0000256
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000303
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsAug 19, 2023The c.3650A>T (p.K1217I) 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 3650, causing the lysine (K) at amino acid position 1217 to be replaced by an isoleucine (I). 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
0.18
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
11
DANN
Benign
0.76
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.00036
N
LIST_S2
Benign
0.19
T;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.35
T
Sift4G
Benign
0.085
T;T
Vest4
0.22
MVP
0.095
MPC
0.0077
ClinPred
0.24
T
GERP RS
-5.8
Varity_R
0.098
gMVP
0.0056

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.

Other links and lift over

dbSNP: rs748109453; hg19: chr19-22154186; API