8-12112907-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001039615.3(ZNF705D):​c.652C>T​(p.His218Tyr) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 6)
Exomes 𝑓: 0.000010 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNF705D
NM_001039615.3 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98
Variant links:
Genes affected
ZNF705D (HGNC:33202): (zinc finger protein 705D) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF705DNM_001039615.3 linkc.652C>T p.His218Tyr missense_variant Exon 7 of 7 ENST00000400085.8 NP_001034704.2 P0CH99

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF705DENST00000400085.8 linkc.652C>T p.His218Tyr missense_variant Exon 7 of 7 5 NM_001039615.3 ENSP00000382957.3 P0CH99

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
51126
Hom.:
0
Cov.:
6
FAILED QC
Gnomad AFR
AF:
0.00
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:
0.0000860
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000104
AC:
9
AN:
863484
Hom.:
0
Cov.:
12
AF XY:
0.00000916
AC XY:
4
AN XY:
436618
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:
0.0000126
Gnomad4 OTH exome
AF:
0.0000261
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000391
AC:
2
AN:
51126
Hom.:
0
Cov.:
6
AF XY:
0.0000425
AC XY:
1
AN XY:
23554
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000860
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.652C>T (p.H218Y) alteration is located in exon 7 (coding exon 5) of the ZNF705D gene. This alteration results from a C to T substitution at nucleotide position 652, causing the histidine (H) at amino acid position 218 to be replaced by a tyrosine (Y). 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
Pathogenic
0.88
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T
Eigen
Uncertain
0.39
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.0042
T
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Uncertain
0.076
D
MutationAssessor
Pathogenic
3.9
H;H
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.52
MutPred
0.89
Loss of disorder (P = 0.0325);Loss of disorder (P = 0.0325);
MVP
0.60
ClinPred
0.99
D
GERP RS
1.0
Varity_R
0.54
gMVP
0.082

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: rs1436692718; hg19: chr8-11970416; API