NM_021922.3:c.-3G>C

Variant names:

• chr6-35452543-G-C
• rs1429194659
• NM_021922.3:c.-3G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021922.3(FANCE):​c.-3G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,165,828 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FANCE NM_021922.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.10
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-3G>C		5_prime_UTR	Exon 1 of 10	NP_068741.1	Q9HB96
	FANCE	NM_001410876.1		c.-3G>C		5_prime_UTR	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.-3G>C		5_prime_UTR	Exon 1 of 10	ENSP00000229769.2	Q9HB96
	FANCE	ENST00000854656.1		c.-3G>C		5_prime_UTR	Exon 1 of 10	ENSP00000524715.1
	FANCE	ENST00000854658.1		c.-3G>C		5_prime_UTR	Exon 1 of 10	ENSP00000524717.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 49124 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 4 AN: 1165828 Hom.: 0 Cov.: 30 AF XY: 0.00000177 AC XY: 1 AN XY: 565152

African (AFR) AF: 0.00 AC: 0 AN: 24632

American (AMR) AF: 0.00 AC: 0 AN: 18106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18396

East Asian (EAS) AF: 0.00 AC: 0 AN: 26954

South Asian (SAS) AF: 0.0000487 AC: 2 AN: 41074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3474

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 961628

Other (OTH) AF: 0.0000213 AC: 1 AN: 46916

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.67
PhyloP100		-2.1
PromoterAI		-0.21	Neutral
Mutation Taster		=300/0	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: rs1429194659; hg19: chr6-35420320;