16-89738853-A-G

Variant names:

• chr16-89738853-A-G
• rs1800359
• NM_001113525.2:c.*607A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113525.2(ZNF276):​c.*607A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 1,613,960 control chromosomes in the GnomAD database, including 353,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41730 hom., cov: 35)
  • Exomes 𝑓: 0.65 (311444 hom.)
• Consequence: ZNF276 NM_001113525.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -6.74
• Publications: 38 publications found

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 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-89738853-A-G is Benign according to our data. Variant chr16-89738853-A-G is described in ClinVar as Benign. ClinVar VariationId is 255266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2	c.*607A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000443381.7	NP_001106997.1
FANCA	NM_000135.4	c.4260+29T>C		intron_variant	Intron 42 of 42	ENST00000389301.8	NP_000126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7	c.*607A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001113525.2	ENSP00000415836.2
FANCA	ENST00000389301.8	c.4260+29T>C		intron_variant	Intron 42 of 42	1	NM_000135.4	ENSP00000373952.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109971 AN: 152144 Hom.: 41663 Cov.: 35

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.668

GnomAD2 exomes AF: 0.702 AC: 176220 AN: 250980 AF XY: 0.695

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.987

Gnomad FIN exome AF: 0.695

Gnomad NFE exome AF: 0.591

Gnomad OTH exome AF: 0.644

GnomAD4 exome AF: 0.646 AC: 943666 AN: 1461698 Hom.: 311444 Cov.: 83 AF XY: 0.648 AC XY: 471318 AN XY: 727120

African (AFR) AF: 0.939 AC: 31430 AN: 33478

American (AMR) AF: 0.776 AC: 34698 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13716 AN: 26132

East Asian (EAS) AF: 0.980 AC: 38907 AN: 39698

South Asian (SAS) AF: 0.802 AC: 69181 AN: 86252

European-Finnish (FIN) AF: 0.685 AC: 36542 AN: 53338

Middle Eastern (MID) AF: 0.651 AC: 3757 AN: 5768

European-Non Finnish (NFE) AF: 0.608 AC: 675833 AN: 1111926

Other (OTH) AF: 0.656 AC: 39602 AN: 60394

GnomAD4 genome AF: 0.723 AC: 110102 AN: 152262 Hom.: 41730 Cov.: 35 AF XY: 0.731 AC XY: 54404 AN XY: 74438

African (AFR) AF: 0.928 AC: 38603 AN: 41578

American (AMR) AF: 0.704 AC: 10765 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5111 AN: 5184

South Asian (SAS) AF: 0.823 AC: 3978 AN: 4832

European-Finnish (FIN) AF: 0.692 AC: 7329 AN: 10594

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40501 AN: 67986

Other (OTH) AF: 0.672 AC: 1420 AN: 2112

Alfa AF: 0.610 Hom.: 16561

Bravo AF: 0.734

Asia WGS AF: 0.904 AC: 3142 AN: 3478

EpiCase AF: 0.583

EpiControl AF: 0.575

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia complementation group A Benign:2

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 10, 2025

GeneKor MSA

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Apr 09, 2019

GeneDx

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.050
DANN	Benign	0.35
PhyloP100		-6.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800359; hg19: chr16-89805261; COSMIC: COSV57066846; COSMIC: COSV57066846;