Genetic Variant ZNF200:c.-481G>A (chr16-3236118-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000575617.1(ZNF200):c.-481G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 148,064 control chromosomes in the GnomAD database, including 13,918 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 0.42 ( 13915 hom., cov: 22)

Exomes 𝑓: 0.41 ( 3 hom. )

Consequence

ZNF200
ENST00000575617.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

10 publications found

Variant links:

Genes affected

ZNF200 (HGNC:12993): (zinc finger protein 200) Predicted to enable metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF200 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000575617.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF200	ENST00000575617.1	TSL:2	c.-481G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000458777.1	I3L1E4
ZNF200	ENST00000575617.1	TSL:2	c.-481G>A	5_prime_UTR	Exon 1 of 3	ENSP00000458777.1	I3L1E4
ZNF200	ENST00000854057.1		c.-566G>A	upstream_gene	N/A	ENSP00000524116.1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

62164

AN:

147920

Hom.:

13903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.526

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.397

Gnomad NFE

AF:

0.474

Gnomad OTH

AF:

0.425

GnomAD4 exome

AF:

0.409

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00109982), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.420

AC:

62204

AN:

148042

Hom.:

13915

Cov.:

AF XY:

0.422

AC XY:

30381

AN XY:

71954

show subpopulations

African (AFR)

AF:

0.256

AC:

10271

AN:

40054

American (AMR)

AF:

0.527

AC:

7783

AN:

14778

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1543

AN:

3458

East Asian (EAS)

AF:

0.572

AC:

2774

AN:

4852

South Asian (SAS)

AF:

0.414

AC:

1885

AN:

4550

European-Finnish (FIN)

AF:

0.477

AC:

4798

AN:

10064

Middle Eastern (MID)

AF:

0.383

AC:

111

AN:

290

European-Non Finnish (NFE)

AF:

0.474

AC:

31799

AN:

67054

Other (OTH)

AF:

0.424

AC:

866

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1557

3114

4672

6229

7786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.451

Hom.:

8613

Bravo

AF:

0.424

Asia WGS

AF:

0.478

AC:

1661

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.36

(source)

DANN

Benign

0.66

PhyloP100

-1.9

PromoterAI

0.074

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over