Genetic Variant ZNF668:c.-513A>G (chr16-31074149-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024706.5(ZNF668):c.-513A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,170 control chromosomes in the GnomAD database, including 11,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 11559 hom., cov: 33)

Exomes 𝑓: 0.43 ( 4 hom. )

Consequence

ZNF668
NM_024706.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

45 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 links:

ZNF646 (HGNC:29004): (zinc finger protein 646) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF646 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZNF668	NM_024706.5 link	c.-513A>G	5_prime_UTR_variant	Exon 1 of 3	ENST00000300849.5	NP_078982.3	Q96K58-1A0A024QZD9
ZNF646	XM_011545990.3 link	c.-80+162T>C	intron_variant	Intron 1 of 2		XP_011544292.1	O15015-2
ZNF646	XM_047434956.1 link	c.-80+1207T>C	intron_variant	Intron 1 of 2		XP_047290912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF668	ENST00000300849.5 link	c.-513A>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_024706.5	ENSP00000300849.4		Q96K58-1
ZNF668	ENST00000564456.1 link	n.36A>G		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56236

AN:

152024

Hom.:

11559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.892

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.429

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.313

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

56241

AN:

152142

Hom.:

11559

Cov.:

AF XY:

0.370

AC XY:

27501

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.263

AC:

10941

AN:

41526

American (AMR)

AF:

0.416

AC:

6353

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1752

AN:

3470

East Asian (EAS)

AF:

0.892

AC:

4616

AN:

5174

South Asian (SAS)

AF:

0.183

AC:

884

AN:

4824

European-Finnish (FIN)

AF:

0.390

AC:

4133

AN:

10590

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26042

AN:

67966

Other (OTH)

AF:

0.435

AC:

914

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1744

3489

5233

6978

8722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.386

Hom.:

17974

Bravo

AF:

0.381

Asia WGS

AF:

0.470

AC:

1637

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

-0.17

PromoterAI

0.064

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over