Variant 19-58211625-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_133502.3(ZNF274):c.918G>A(p.Pro306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 1,613,794 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 60 hom. )

Consequence

ZNF274
NM_133502.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.76

Variant links:

Genes affected

ZNF274 (HGNC:13068): (zinc finger protein 274) This gene encodes a zinc finger protein containing five C2H2-type zinc finger domains, one or two Kruppel-associated box A (KRAB A) domains, and a leucine-rich domain. The encoded protein has been suggested to be a transcriptional repressor. It localizes predominantly to the nucleolus. Alternatively spliced transcript variants encoding different isoforms exist. These variants utilize alternative polyadenylation signals. [provided by RefSeq, Jul 2008]

ZNF274 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-58211625-G-A is Benign according to our data. Variant chr19-58211625-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650583.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.76 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF274	NM_133502.3 linkuse as main transcript	c.918G>A	p.Pro306=	synonymous_variant	7/8	ENST00000617501.5	NP_598009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF274	ENST00000617501.5 linkuse as main transcript	c.918G>A	p.Pro306=	synonymous_variant	7/8	1	NM_133502.3	ENSP00000484810	P1	Q96GC6-1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

665

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00461

AC:

1155

AN:

250432

Hom.:

AF XY:

0.00499

AC XY:

677

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00773

Gnomad OTH exome

AF:

0.00559

GnomAD4 exome

AF:

0.00741

AC:

10837

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

5270

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00246

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00368

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00880

Gnomad4 OTH exome

AF:

0.00773

GnomAD4 genome

AF:

0.00437

AC:

665

AN:

152278

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

316

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00707

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00819

EpiControl

AF:

0.00902

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ZNF274: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.64

DANN

Benign

0.79

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