16-3236118-C-T

Variant names:

• chr16-3236118-C-T
• rs442387
• ENST00000575617.1:c.-481G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 10 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF200	ENST00000575617.1	c.-481G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	2		ENSP00000458777.1
ZNF200	ENST00000575617.1	c.-481G>A		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000458777.1
ZNF200	ENST00000577015.1	n.-115G>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 62164 AN: 147920 Hom.: 13903 Cov.: 22

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: 9 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.375 AC XY: 6 AN XY: 16

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 4 AN: 12

Other (OTH) AF: 1.00 AC: 4 AN: 4

⚠️ 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.

GnomAD4 genome AF: 0.420 AC: 62204 AN: 148042 Hom.: 13915 Cov.: 22 AF XY: 0.422 AC XY: 30381 AN XY: 71954

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.66
PhyloP100		-1.9
PromoterAI		0.074	Neutral

Splicing

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

Other links and lift over

dbSNP: rs442387; hg19: chr16-3286118;