chr20-53571837-T-A

Position:

• chr20-53571837-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006526.3(ZNF217):​c.3054A>T​(p.Ser1018Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,608,894 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (71 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: ZNF217 NM_006526.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.68

Genes affected

ZNF217 (HGNC:13009): (zinc finger protein 217) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in mitochondrion and nuclear speck. Part of histone deacetylase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000197670 (HGNC:56842): (ZNF217 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-53571837-T-A is Benign according to our data. Variant chr20-53571837-T-A is described in ClinVar as [Benign]. Clinvar id is 791210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF217	NM_006526.3	c.3054A>T	p.Ser1018Ser	synonymous_variant	5/6	ENST00000371471.7	NP_006517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF217	ENST00000371471.7	c.3054A>T	p.Ser1018Ser	synonymous_variant	5/6	5	NM_006526.3	ENSP00000360526.2
ZNF217	ENST00000302342.3	c.3054A>T	p.Ser1018Ser	synonymous_variant	4/5	1		ENSP00000304308.3
ZNF217	ENST00000437222.1	c.302-2573A>T		intron_variant		2		ENSP00000394010.1
ENSG00000197670	ENST00000424252.2	n.788-811T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2381 AN: 151888 Hom.: 71 Cov.: 30

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00408 AC: 990 AN: 242624 Hom.: 19 AF XY: 0.00295 AC XY: 387 AN XY: 131304

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000350

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000361

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00156 AC: 2267 AN: 1456888 Hom.: 64 Cov.: 30 AF XY: 0.00134 AC XY: 969 AN XY: 724712

Gnomad4 AFR exome AF: 0.0598

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.00264

GnomAD4 genome AF: 0.0157 AC: 2387 AN: 152006 Hom.: 71 Cov.: 30 AF XY: 0.0149 AC XY: 1107 AN XY: 74306

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.00394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00141 Hom.: 2

Bravo AF: 0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.038
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs36029677; hg19: chr20-52188376;