Variant chr8-12112775-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039615.3(ZNF705D):c.520T>C(p.Cys174Arg) 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 0.00010 ( 0 hom., cov: 3)

Exomes 𝑓: 0.000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705D
NM_001039615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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]

ZNF705D links:

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, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705D	NM_001039615.3 linkuse as main transcript	c.520T>C	p.Cys174Arg	missense_variant	7/7	ENST00000400085.8	NP_001034704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705D	ENST00000400085.8 linkuse as main transcript	c.520T>C	p.Cys174Arg	missense_variant	7/7	5	NM_001039615.3	ENSP00000382957	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

10044

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000222

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000460

AC:

AN:

325972

Hom.:

Cov.:

AF XY:

0.0000475

AC XY:

AN XY:

168402

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.0000951

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:

0.00

Gnomad4 OTH exome

AF:

0.000158

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000996

AC:

AN:

10044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4420

show subpopulations

Gnomad4 AFR

AF:

0.000222

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

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

Oct 29, 2021

The c.520T>C (p.C174R) alteration is located in exon 7 (coding exon 5) of the ZNF705D gene. This alteration results from a T to C substitution at nucleotide position 520, causing the cysteine (C) at amino acid position 174 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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.39

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.0060

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.5

H;H

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-12

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.025

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.95

P;P

Vest4

0.51

MutPred

0.90

Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);

MVP

0.79

ClinPred

0.97

GERP RS

1.0

Varity_R

0.30

gMVP

0.076

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