Variant 1-248850411-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_017865.4(ZNF692):c.1359C>T(p.Cys453=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,614,154 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 62 hom. )

Consequence

ZNF692
NM_017865.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.703

Variant links:

Genes affected

ZNF692 (HGNC:26049): (zinc finger protein 692) 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 and regulation of gluconeogenesis. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF692 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 1-248850411-G-A is Benign according to our data. Variant chr1-248850411-G-A is described in ClinVar as [Benign]. Clinvar id is 788693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.703 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00525 (800/152340) while in subpopulation AMR AF= 0.0419 (642/15306). AF 95% confidence interval is 0.0393. There are 14 homozygotes in gnomad4. There are 451 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF692	NM_017865.4 linkuse as main transcript	c.1359C>T	p.Cys453=	synonymous_variant	12/12	ENST00000306601.9	NP_060335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF692	ENST00000306601.9 linkuse as main transcript	c.1359C>T	p.Cys453=	synonymous_variant	12/12	1	NM_017865.4	ENSP00000305483	P2	Q9BU19-1

Frequencies

GnomAD3 genomes

AF:

0.00519

AC:

790

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0413

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00625

AC:

1570

AN:

251344

Hom.:

AF XY:

0.00535

AC XY:

727

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00581

Gnomad FIN exome

AF:

0.000509

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00224

AC:

3279

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1617

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.0388

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.00619

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.000656

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00525

AC:

800

AN:

152340

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

451

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.0419

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00816

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jan 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.6

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over