Variant rs8046978 details in Genebe, Genetics Data Aggregator

Variant summary

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

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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2520 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35363 hom. )

Consequence

ZNF668
NM_024706.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF668	NM_024706.5 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	3/3	ENST00000300849.5	NP_078982.3
ZNF668	NM_001172669.2 linkuse as main transcript	c.1409C>T	p.Ala470Val	missense_variant	4/4		NP_001166140.1
ZNF668	NM_001172668.2 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	3/3		NP_001166139.1
ZNF668	NM_001172670.2 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	3/3		NP_001166141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF668	ENST00000300849.5 linkuse as main transcript	c.1340C>T	p.Ala447Val	missense_variant	3/3	1	NM_024706.5	ENSP00000300849	P1
	ENST00000622229.1 linkuse as main transcript	n.2165G>A		non_coding_transcript_exon_variant	2/2	2

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

GnomAD3 exomes

AF:

0.163

AC:

39496

AN:

242504

Hom.:

4008

AF XY:

0.167

AC XY:

22088

AN XY:

132388

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 SAS exome

AF:

0.114

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

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.00166

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.163

AC:

24839

AN:

152184

Hom.:

2520

Cov.:

AF XY:

0.161

AC XY:

12000

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0622

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.198

Hom.:

1520

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

DANN

Benign

0.97

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

.;.;T;.;.;.

MetaRNN

Benign

0.0033

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.40

N;N;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.33

T;T;T;T;T;T

Sift4G

Benign

0.55

T;T;T;T;T;T

Vest4

0.042

MPC

0.84

ClinPred

0.0052

GERP RS

-1.8

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over