Genetic Variant ZNF705A:p.Arg189Trp (chr12-8177245-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001004328.3(ZNF705A):c.565C>T(p.Arg189Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,611,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ZNF705A
NM_001004328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.93

Publications

1 publications found

Variant links:

Genes affected

ZNF705A (HGNC:32281): (zinc finger protein 705A) 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. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF705A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004328.3. 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
	ZNF705A	NM_001004328.3	MANE Select	c.565C>T	p.Arg189Trp	missense	Exon 6 of 6	NP_001004328.1	Q6ZN79

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF705A	ENST00000396570.8	TSL:5 MANE Select	c.565C>T	p.Arg189Trp	missense	Exon 6 of 6	ENSP00000379816.4	Q6ZN79
ZNF705A	ENST00000359286.4	TSL:2	c.565C>T	p.Arg189Trp	missense	Exon 5 of 5	ENSP00000352233.4	Q6ZN79
ZNF705A	ENST00000610508.4	TSL:5	c.565C>T	p.Arg189Trp	missense	Exon 6 of 6	ENSP00000481663.1	Q6ZN79

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

250278

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.000942

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000815

AC:

119

AN:

1459406

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

725972

show subpopulations

African (AFR)

AF:

0.000779

AC:

AN:

33390

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.000267

AC:

AN:

86150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

1111596

Other (OTH)

AF:

0.000116

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

AF:

0.000315

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00104

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000416

ExAC

AF:

0.000140

AC:

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

Uncertain

0.42

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.8

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.14

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.18

M_CAP

Benign

0.0017

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

-2.9

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.039

Sift

Uncertain

0.0080

Sift4G

Benign

0.069

Polyphen

0.0020

Vest4

0.10

MVP

0.18

MPC

1.4

ClinPred

0.025

GERP RS

-2.7

Varity_R

0.050

gMVP

0.060

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over