rs1061646

Positions:

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: 0.398

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr16-89739569-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2 link	c.*1323G>A		3_prime_UTR_variant	11/11	ENST00000443381.7	NP_001106997.1	Q8N554-1I6L9I3
FANCA	NM_000135.4 link	c.3935-16C>T		intron_variant		ENST00000389301.8	NP_000126.2	O15360-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 link	c.*1323G>A		3_prime_UTR_variant	11/11	1	NM_001113525.2	ENSP00000415836.2		Q8N554-1
FANCA	ENST00000389301.8 link	c.3935-16C>T		intron_variant		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

GnomAD3 exomes

AF:

0.425

AC:

65869

AN:

155154

Hom.:

16003

AF XY:

0.417

AC XY:

34144

AN XY:

81922

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 SAS exome

AF:

0.471

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

Gnomad4 AFR exome

AF:

0.546

Gnomad4 AMR exome

AF:

0.596

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.475

Gnomad4 FIN exome

AF:

0.388

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.410

AC:

62394

AN:

152058

Hom.:

14131

Cov.:

AF XY:

0.422

AC XY:

31343

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.743

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.395

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.315

Hom.:

8974

Bravo

AF:

0.425

Asia WGS

AF:

0.610

AC:

2120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Fanconi anemia complementation group A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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