Variant 8-12112923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039615.3(ZNF705D):c.668C>T(p.Thr223Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 6)

Exomes 𝑓: 0.00052 ( 51 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705D
NM_001039615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20533615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705D	NM_001039615.3 linkuse as main transcript	c.668C>T	p.Thr223Met	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.668C>T	p.Thr223Met	missense_variant	7/7	5	NM_001039615.3	ENSP00000382957	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

122

AN:

53654

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000320

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:

0.0000808

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000518

AC:

499

AN:

962476

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

295

AN XY:

484664

show subpopulations

Gnomad4 AFR exome

AF:

0.00648

Gnomad4 AMR exome

AF:

0.000490

Gnomad4 ASJ exome

AF:

0.0000543

Gnomad4 EAS exome

AF:

0.0000995

Gnomad4 SAS exome

AF:

0.00371

Gnomad4 FIN exome

AF:

0.0000255

Gnomad4 NFE exome

AF:

0.0000878

Gnomad4 OTH exome

AF:

0.000384

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00227

AC:

122

AN:

53730

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

AN XY:

24780

show subpopulations

Gnomad4 AFR

AF:

0.00600

Gnomad4 AMR

AF:

0.000320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000809

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00202

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

Aug 12, 2021

The c.668C>T (p.T223M) 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 668, causing the threonine (T) at amino acid position 223 to be replaced by a methionine (M). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.0

DANN

Benign

0.88

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

M;M

MutationTaster

Benign

0.85

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.086

Sift

Uncertain

0.010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.15

B;B

Vest4

0.27

MutPred

0.62

Gain of methylation at K220 (P = 0.0958);Gain of methylation at K220 (P = 0.0958);

MVP

0.10

ClinPred

0.59

GERP RS

1.0

Varity_R

0.055

gMVP

0.019

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