dbSNP rs1303839762: ZNF705D:p.Gln232Lys (chr8-12112949-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039615.3(ZNF705D):c.694C>A(p.Gln232Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000033 ( 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: -2.20

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15161094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039615.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF705D	NM_001039615.3	MANE Select	c.694C>A	p.Gln232Lys	missense	Exon 7 of 7	NP_001034704.2	P0CH99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF705D	ENST00000400085.8	TSL:5 MANE Select	c.694C>A	p.Gln232Lys	missense	Exon 7 of 7	ENSP00000382957.3	P0CH99

Frequencies

GnomAD3 genomes

AF:

0.0000170

AC:

AN:

58784

Hom.:

Cov.:

show subpopulations

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:

0.0000367

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000334

AC:

AN:

1079242

Hom.:

Cov.:

AF XY:

0.0000350

AC XY:

AN XY:

542988

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000676

AC:

AN:

29606

American (AMR)

AF:

0.00

AC:

AN:

29362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20302

East Asian (EAS)

AF:

0.00

AC:

AN:

31786

South Asian (SAS)

AF:

0.00

AC:

AN:

67054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3078

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

808902

Other (OTH)

AF:

0.0000436

AC:

AN:

45924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.289

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000170

AC:

AN:

58784

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

27250

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21356

American (AMR)

AF:

0.00

AC:

AN:

3534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1292

East Asian (EAS)

AF:

0.00

AC:

AN:

1132

South Asian (SAS)

AF:

0.00

AC:

AN:

918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000367

AC:

AN:

27264

Other (OTH)

AF:

0.00

AC:

AN:

592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.5

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.027

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.33

M_CAP

Benign

0.0010

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.52

PhyloP100

-2.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

REVEL

Benign

0.029

Sift

Benign

0.18

Sift4G

Benign

0.28

Polyphen

0.080

Vest4

0.16

MutPred

0.54

Gain of methylation at Q232 (P = 3e-04)

MVP

0.048

ClinPred

0.085

GERP RS

0.073

Varity_R

0.091

gMVP

0.017

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over