chr6-35452441-C-T

Variant names:

• chr6-35452441-C-T
• rs886061326
• NM_021922.3:c.-105C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021922.3(FANCE):​c.-105C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000933 in 1,136,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: FANCE NM_021922.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

FANCE (HGNC:3586): (FA complementation group E) 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 E. [provided by RefSeq, Jul 2008]

FANCE Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group E

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	NM_021922.3	MANE Select	c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_068741.1	Q9HB96
	FANCE	NM_021922.3	MANE Select	c.-105C>T		5_prime_UTR	Exon 1 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001397805.1	A0A8Q3WL50

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000229769.3	TSL:1 MANE Select	c.-105C>T		5_prime_UTR	Exon 1 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000854656.1		c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000524715.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000823 AC: 81 AN: 984236 Hom.: 0 Cov.: 16 AF XY: 0.0000774 AC XY: 36 AN XY: 465096

African (AFR) AF: 0.0000981 AC: 2 AN: 20384

American (AMR) AF: 0.00 AC: 0 AN: 7062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12444

East Asian (EAS) AF: 0.0000415 AC: 1 AN: 24120

South Asian (SAS) AF: 0.00 AC: 0 AN: 17388

European-Finnish (FIN) AF: 0.000106 AC: 2 AN: 18938

Middle Eastern (MID) AF: 0.000380 AC: 1 AN: 2634

European-Non Finnish (NFE) AF: 0.0000867 AC: 73 AN: 842246

Other (OTH) AF: 0.0000513 AC: 2 AN: 39020

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000486 Hom.: 0

Bravo AF: 0.000125

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fanconi anemia complementation group E (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.96
PhyloP100		1.2
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs886061326; hg19: chr6-35420218;