Variant 8-12109988-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039615.3(ZNF705D):c.101A>T(p.Asp34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.017 ( 0 hom., cov: 0)

Exomes 𝑓: 0.12 ( 163 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705D
NM_001039615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015824646).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705D	NM_001039615.3 linkuse as main transcript	c.101A>T	p.Asp34Val	missense_variant	4/7	ENST00000400085.8	NP_001034704.2	P0CH99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705D	ENST00000400085.8 linkuse as main transcript	c.101A>T	p.Asp34Val	missense_variant	4/7	5	NM_001039615.3	ENSP00000382957.3		P0CH99

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

4734

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0160

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.0417

GnomAD3 exomes

AF:

0.00407

AC:

AN:

2454

Hom.:

AF XY:

0.000833

AC XY:

AN XY:

1200

show subpopulations

Gnomad AFR exome

AF:

0.0161

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.117

AC:

4310

AN:

36842

Hom.:

163

Cov.:

AF XY:

0.115

AC XY:

2153

AN XY:

18740

show subpopulations

Gnomad4 AFR exome

AF:

0.0432

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.0427

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0970

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0173

AC:

AN:

4742

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

AN XY:

2116

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0333

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0198

Gnomad4 OTH

AF:

0.0429

Alfa

AF:

0.0731

Hom.:

ExAC

AF:

0.00101

AC:

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

Jul 13, 2021

The c.101A>T (p.D34V) alteration is located in exon 4 (coding exon 2) of the ZNF705D gene. This alteration results from a A to T substitution at nucleotide position 101, causing the aspartic acid (D) at amino acid position 34 to be replaced by a valine (V). 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

0.75

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.23

.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.50

MutPred

0.70

Gain of MoRF binding (P = 0.0374);Gain of MoRF binding (P = 0.0374);

MVP

0.40

ClinPred

0.24

GERP RS

0.83

Varity_R

0.59

gMVP

0.022

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