19-11905402-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001364730.1(ZNF69):c.1005G>A(p.Thr335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,614,136 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (14 hom.)
• Consequence: ZNF69 NM_001364730.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.82

Genes affected

ZNF69 (HGNC:13138): (zinc finger protein 69) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-11905402-G-A is Benign according to our data. Variant chr19-11905402-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF69	NM_001364730.1	c.1005G>A	p.Thr335=	synonymous_variant	4/4	ENST00000429654.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF69	ENST00000429654.7	c.1005G>A	p.Thr335=	synonymous_variant	4/4	2	NM_001364730.1	P1
ZNF69	ENST00000340180.5	c.448+515G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00220 AC: 552 AN: 251342 Hom.: 0 AF XY: 0.00230 AC XY: 313 AN XY: 135846

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00222

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00344 AC: 5024 AN: 1461850 Hom.: 14 Cov.: 31 AF XY: 0.00341 AC XY: 2477 AN XY: 727222

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.00402

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.00225 AC: 342 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74464

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00382

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00262 Hom.: 0

Bravo AF: 0.00213

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00308

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ZNF69: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.4
Dann	Benign	0.31

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

Other links and lift over

dbSNP: rs191881165; hg19: chr19-12016217;