16-89739939-A-T

Position:

• chr16-89739939-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.708

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-89739939-A-T is Benign according to our data. Variant chr16-89739939-A-T is described in ClinVar as [Benign]. Clinvar id is 135541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89739939-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.*1693A>T		3_prime_UTR_variant	11/11	ENST00000443381.7	NP_001106997.1
FANCA	NM_000135.4	c.3934+55T>A		intron_variant		ENST00000389301.8	NP_000126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.*1693A>T		3_prime_UTR_variant	11/11	1	NM_001113525.2	ENSP00000415836.2
FANCA	ENST00000389301.8	c.3934+55T>A		intron_variant		1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82415 AN: 152026 Hom.: 24964 Cov.: 33

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

GnomAD3 exomes AF: 0.523 AC: 130329 AN: 249378 Hom.: 38768 AF XY: 0.509 AC XY: 68676 AN XY: 134800

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 SAS exome AF: 0.590

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.: 41 AF XY: 0.452 AC XY: 325709 AN XY: 720902

Gnomad4 AFR exome AF: 0.775

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.588

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.468

GnomAD4 genome AF: 0.542 AC: 82527 AN: 152144 Hom.: 25010 Cov.: 33 AF XY: 0.551 AC XY: 40988 AN XY: 74358

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.480

Alfa AF: 0.445 Hom.: 3054

Bravo AF: 0.559

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

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	Apr 09, 2019	- -

Fanconi anemia complementation group A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs7195906; hg19: chr16-89806347; COSMIC: COSV57065786; COSMIC: COSV57065786;