NM_001113525.2:c.*1693A>T

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.*1693A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,604,774 control chromosomes in the GnomAD database, including 184,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 25010 hom., cov: 33)

Exomes 𝑓: 0.45 ( 159056 hom. )

Consequence

ZNF276
NM_001113525.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.708

Publications

27 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=0.084).

BP6

Variant 16-89739939-A-T is Benign according to our data. Variant chr16-89739939-A-T is described in ClinVar as Benign. ClinVar VariationId is 135541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113525.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF276	NM_001113525.2	MANE Select	c.*1693A>T	3_prime_UTR	Exon 11 of 11	NP_001106997.1
FANCA	NM_000135.4	MANE Select	c.3934+55T>A	intron	N/A	NP_000126.2
ZNF276	NM_152287.4		c.*1693A>T	3_prime_UTR	Exon 11 of 11	NP_689500.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZNF276	ENST00000443381.7	TSL:1 MANE Select	c.*1693A>T	3_prime_UTR	Exon 11 of 11	ENSP00000415836.2
ZNF276	ENST00000289816.9	TSL:1	c.*1693A>T	3_prime_UTR	Exon 11 of 11	ENSP00000289816.5
FANCA	ENST00000389301.8	TSL:1 MANE Select	c.3934+55T>A	intron	N/A	ENSP00000373952.3

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82415

AN:

152026

Hom.:

24964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.310

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.474

GnomAD2 exomes

AF:

0.523

AC:

130329

AN:

249378

AF XY:

0.509

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.983

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.451

AC:

654763

AN:

1452630

Hom.:

159056

Cov.:

AF XY:

0.452

AC XY:

325709

AN XY:

720902

show subpopulations

African (AFR)

AF:

0.775

AC:

25754

AN:

33218

American (AMR)

AF:

0.653

AC:

28829

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8243

AN:

25888

East Asian (EAS)

AF:

0.978

AC:

38594

AN:

39462

South Asian (SAS)

AF:

0.588

AC:

50565

AN:

85924

European-Finnish (FIN)

AF:

0.469

AC:

24963

AN:

53210

Middle Eastern (MID)

AF:

0.340

AC:

1949

AN:

5726

European-Non Finnish (NFE)

AF:

0.405

AC:

447833

AN:

1105140

Other (OTH)

AF:

0.468

AC:

28033

AN:

59882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17637

35274

52910

70547

88184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14514

29028

43542

58056

72570

<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:

0.542

AC:

82527

AN:

152144

Hom.:

25010

Cov.:

AF XY:

0.551

AC XY:

40988

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.762

AC:

31641

AN:

41508

American (AMR)

AF:

0.551

AC:

8419

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1119

AN:

3472

East Asian (EAS)

AF:

0.980

AC:

5077

AN:

5178

South Asian (SAS)

AF:

0.623

AC:

3005

AN:

4822

European-Finnish (FIN)

AF:

0.481

AC:

5087

AN:

10582

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26810

AN:

67978

Other (OTH)

AF:

0.480

AC:

1013

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1738

3475

5213

6950

8688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.445

Hom.:

3054

Bravo

AF:

0.559

Asia WGS

AF:

0.793

AC:

2757

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Fanconi anemia complementation group A (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.93

(source)

DANN

Benign

0.58

PhyloP100

-0.71

PromoterAI

-0.0043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over