Variant chr8-12112953-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001039615.3(ZNF705D):c.698G>A(p.Cys233Tyr) 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 0.000034 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000051 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705D
NM_001039615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705D	NM_001039615.3 linkuse as main transcript	c.698G>A	p.Cys233Tyr	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.698G>A	p.Cys233Tyr	missense_variant	7/7	5	NM_001039615.3	ENSP00000382957	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

59614

Hom.:

Cov.:

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:

0.0000362

Gnomad OTH

AF:

0.00168

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000510

AC:

AN:

1097924

Hom.:

Cov.:

AF XY:

0.0000435

AC XY:

AN XY:

551830

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:

0.000161

Gnomad4 NFE exome

AF:

0.0000412

Gnomad4 OTH exome

AF:

0.000322

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000335

AC:

AN:

59614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27740

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:

0.0000362

Gnomad4 OTH

AF:

0.00168

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

Feb 28, 2024

The c.698G>A (p.C233Y) alteration is located in exon 7 (coding exon 5) of the ZNF705D gene. This alteration results from a G to A substitution at nucleotide position 698, causing the cysteine (C) at amino acid position 233 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

0.77

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.0084

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

4.3

H;H

MutationTaster

Benign

0.71

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-11

D;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.018

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0010

B;B

Vest4

0.56

MutPred

0.81

Loss of disorder (P = 0.0663);Loss of disorder (P = 0.0663);

MVP

0.60

ClinPred

0.45

GERP RS

1.0

Varity_R

0.42

gMVP

0.047

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