NM_001113525.2:c.*1689C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001113525.2(ZNF276):c.*1689C>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 0.0965 in 1,605,564 control chromosomes in the GnomAD database, including 8,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1015 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7229 hom. )

Consequence

ZNF276
NM_001113525.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0200

Publications

13 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.032).

BP6

Variant 16-89739935-C-A is Benign according to our data. Variant chr16-89739935-C-A is described in ClinVar as Benign. ClinVar VariationId is 135540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2 link	c.*1689C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000443381.7	NP_001106997.1
FANCA	NM_000135.4 link	c.3934+59G>T		intron_variant	Intron 39 of 42	ENST00000389301.8	NP_000126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 link	c.*1689C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001113525.2	ENSP00000415836.2
FANCA	ENST00000389301.8 link	c.3934+59G>T		intron_variant	Intron 39 of 42	1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16288

AN:

152126

Hom.:

1010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0792

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0716

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.0975

GnomAD2 exomes

AF:

0.0954

AC:

23782

AN:

249270

AF XY:

0.0956

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.0759

Gnomad EAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.0724

Gnomad NFE exome

AF:

0.0870

Gnomad OTH exome

AF:

0.0783

GnomAD4 exome

AF:

0.0954

AC:

138574

AN:

1453320

Hom.:

7229

Cov.:

AF XY:

0.0958

AC XY:

69088

AN XY:

721400

show subpopulations

African (AFR)

AF:

0.149

AC:

4949

AN:

33260

American (AMR)

AF:

0.0340

AC:

1505

AN:

44298

Ashkenazi Jewish (ASJ)

AF:

0.0751

AC:

1943

AN:

25856

East Asian (EAS)

AF:

0.165

AC:

6526

AN:

39474

South Asian (SAS)

AF:

0.111

AC:

9550

AN:

85866

European-Finnish (FIN)

AF:

0.0703

AC:

3738

AN:

53196

Middle Eastern (MID)

AF:

0.0588

AC:

337

AN:

5732

European-Non Finnish (NFE)

AF:

0.0938

AC:

103737

AN:

1105682

Other (OTH)

AF:

0.105

AC:

6289

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6214

12428

18641

24855

31069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3984

7968

11952

15936

19920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16313

AN:

152244

Hom.:

1015

Cov.:

AF XY:

0.105

AC XY:

7799

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.147

AC:

6090

AN:

41542

American (AMR)

AF:

0.0559

AC:

855

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0792

AC:

275

AN:

3472

East Asian (EAS)

AF:

0.223

AC:

1154

AN:

5172

South Asian (SAS)

AF:

0.126

AC:

609

AN:

4830

European-Finnish (FIN)

AF:

0.0716

AC:

759

AN:

10606

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0931

AC:

6331

AN:

68010

Other (OTH)

AF:

0.0979

AC:

207

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

752

1503

2255

3006

3758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0937

Hom.:

1431

Bravo

AF:

0.107

Asia WGS

AF:

0.169

AC:

587

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

(source)

DANN

Benign

0.66

PhyloP100

0.020

PromoterAI

-0.028

Neutral

(source)

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.

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