rs1061646

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001113525.2(ZNF276):c.*1323G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,550,080 control chromosomes in the GnomAD database, including 107,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14131 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93088 hom. )

Consequence

ZNF276
NM_001113525.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.398

Publications

36 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-89739569-G-A is Benign according to our data. Variant chr16-89739569-G-A is described in ClinVar as [Benign]. Clinvar id is 255264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2 link	c.*1323G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000443381.7	NP_001106997.1	Q8N554-1I6L9I3
FANCA	NM_000135.4 link	c.3935-16C>T		intron_variant	Intron 39 of 42	ENST00000389301.8	NP_000126.2	O15360-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 link	c.*1323G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001113525.2	ENSP00000415836.2		Q8N554-1
FANCA	ENST00000389301.8 link	c.3935-16C>T		intron_variant	Intron 39 of 42	1	NM_000135.4	ENSP00000373952.3		O15360-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62320

AN:

151940

Hom.:

14112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.395

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.425

AC:

65869

AN:

155154

AF XY:

0.417

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.725

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.349

AC:

487419

AN:

1398022

Hom.:

93088

Cov.:

AF XY:

0.350

AC XY:

241644

AN XY:

689600

show subpopulations

African (AFR)

AF:

0.546

AC:

17226

AN:

31578

American (AMR)

AF:

0.596

AC:

21291

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

5987

AN:

25176

East Asian (EAS)

AF:

0.808

AC:

28870

AN:

35736

South Asian (SAS)

AF:

0.475

AC:

37634

AN:

79218

European-Finnish (FIN)

AF:

0.388

AC:

18872

AN:

48650

Middle Eastern (MID)

AF:

0.265

AC:

1503

AN:

5672

European-Non Finnish (NFE)

AF:

0.311

AC:

335409

AN:

1078310

Other (OTH)

AF:

0.356

AC:

20627

AN:

57978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17097

34194

51292

68389

85486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.410

AC:

62394

AN:

152058

Hom.:

14131

Cov.:

AF XY:

0.422

AC XY:

31343

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.538

AC:

22319

AN:

41450

American (AMR)

AF:

0.485

AC:

7411

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

821

AN:

3468

East Asian (EAS)

AF:

0.743

AC:

3821

AN:

5146

South Asian (SAS)

AF:

0.492

AC:

2369

AN:

4818

European-Finnish (FIN)

AF:

0.395

AC:

4187

AN:

10596

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.300

AC:

20377

AN:

67976

Other (OTH)

AF:

0.367

AC:

775

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1769

3538

5308

7077

8846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.344

Hom.:

16380

Bravo

AF:

0.425

Asia WGS

AF:

0.610

AC:

2120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group A

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

(source)

DANN

Benign

0.44

PhyloP100

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1061646

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