rs8046978

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024706.5(ZNF668):c.1340C>T(p.Ala447Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,608,640 control chromosomes in the GnomAD database, including 37,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2520 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35363 hom. )

Consequence

ZNF668
NM_024706.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.299

Publications

15 publications found

Variant links:

Genes affected

ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF668 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ZNF668 links:

ENSG00000232748 (HGNC:):

ENSG00000232748 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032924712).

BP6

Variant 16-31061588-G-A is Benign according to our data. Variant chr16-31061588-G-A is described in ClinVar as Benign. ClinVar VariationId is 3911168.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF668	NM_024706.5	MANE Select	c.1340C>T	p.Ala447Val	missense	Exon 3 of 3	NP_078982.3
ZNF668	NM_001172669.2		c.1409C>T	p.Ala470Val	missense	Exon 4 of 4	NP_001166140.1
ZNF668	NM_001172668.2		c.1340C>T	p.Ala447Val	missense	Exon 3 of 3	NP_001166139.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ZNF668	ENST00000300849.5	TSL:1 MANE Select	c.1340C>T	p.Ala447Val	missense	Exon 3 of 3	ENSP00000300849.4
ZNF668	ENST00000426488.6	TSL:5	c.1409C>T	p.Ala470Val	missense	Exon 4 of 4	ENSP00000403975.2
ZNF668	ENST00000539836.3	TSL:5	c.1409C>T	p.Ala470Val	missense	Exon 4 of 4	ENSP00000442573.3

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24836

AN:

152066

Hom.:

2520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.164

GnomAD2 exomes

AF:

0.163

AC:

39496

AN:

242504

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.211

AC:

307466

AN:

1456456

Hom.:

35363

Cov.:

AF XY:

0.209

AC XY:

151810

AN XY:

724810

show subpopulations

African (AFR)

AF:

0.0533

AC:

1785

AN:

33472

American (AMR)

AF:

0.109

AC:

4852

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3690

AN:

26090

East Asian (EAS)

AF:

0.00166

AC:

AN:

39688

South Asian (SAS)

AF:

0.117

AC:

10085

AN:

86226

European-Finnish (FIN)

AF:

0.220

AC:

10647

AN:

48474

Middle Eastern (MID)

AF:

0.172

AC:

991

AN:

5766

European-Non Finnish (NFE)

AF:

0.237

AC:

263697

AN:

1111716

Other (OTH)

AF:

0.193

AC:

11653

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17109

34219

51328

68438

85547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8746

17492

26238

34984

43730

<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:

0.163

AC:

24839

AN:

152184

Hom.:

2520

Cov.:

AF XY:

0.161

AC XY:

12000

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0622

AC:

2584

AN:

41558

American (AMR)

AF:

0.161

AC:

2459

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

531

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5174

South Asian (SAS)

AF:

0.104

AC:

501

AN:

4830

European-Finnish (FIN)

AF:

0.228

AC:

2410

AN:

10584

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15775

AN:

67962

Other (OTH)

AF:

0.162

AC:

341

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1028

2056

3084

4112

5140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.190

Hom.:

2048

Bravo

AF:

0.152

TwinsUK

AF:

0.242

AC:

897

ALSPAC

AF:

0.250

AC:

963

ESP6500AA

AF:

0.0586

AC:

257

ESP6500EA

AF:

0.228

AC:

1956

ExAC

AF:

0.162

AC:

19537

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

(source)

DANN

Benign

0.97

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.91

PhyloP100

0.30

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.40

REVEL

Benign

0.035

Sift

Benign

0.33

Sift4G

Benign

0.55

Vest4

0.042

MPC

0.84

ClinPred

0.0052

GERP RS

-1.8

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over