16-89727323-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001113525.2(ZNF276):c.1051C>T(p.Arg351Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00858 in 1,613,734 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 82 hom. )

Consequence

ZNF276
NM_001113525.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.33

Publications

17 publications found

Variant links:

Genes affected

ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ZNF276 links:

FANCA (HGNC:3582): (FA complementation group A) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

Fanconi anemia complementation group A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058114827).

BP6

Variant 16-89727323-C-T is Benign according to our data. Variant chr16-89727323-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647133.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2 link	c.1051C>T	p.Arg351Trp	missense_variant	Exon 5 of 11	ENST00000443381.7	NP_001106997.1	Q8N554-1I6L9I3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 link	c.1051C>T	p.Arg351Trp	missense_variant	Exon 5 of 11	1	NM_001113525.2	ENSP00000415836.2		Q8N554-1

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

961

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00748

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00969

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00535

AC:

1345

AN:

251440

AF XY:

0.00538

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00425

Gnomad NFE exome

AF:

0.00846

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00881

AC:

12881

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

6191

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33480

American (AMR)

AF:

0.00414

AC:

185

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00712

AC:

186

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000487

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00495

AC:

264

AN:

53372

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11586

AN:

1111800

Other (OTH)

AF:

0.00934

AC:

564

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

664

1328

1993

2657

3321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00632

AC:

962

AN:

152124

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00219

AC:

AN:

41498

American (AMR)

AF:

0.00747

AC:

114

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00473

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00969

AC:

659

AN:

68018

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00800

Hom.:

Bravo

AF:

0.00594

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00523

AC:

635

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00782

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF276: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

.;M

PhyloP100

5.3

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.045

D;D

Polyphen

1.0

.;D

Vest4

0.72

MVP

0.13

MPC

0.11

ClinPred

0.021

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.30

Mutation Taster

=46/54

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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16-89727323-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over