rs587778328

Variant names:

• chr9-95111279-CAGG-C
• rs587778328
• ENST00000490972.7:c.1393_1395delCCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_Supporting BP6

The NM_001243744.2(FANCC):​c.1393_1395delCCT​(p.Pro465del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,559,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: FANCC NM_001243744.2 conservative_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided U:1 B:1 O:1
• Conservation: PhyloP100: 0.0340
• Publications: 1 publications found

Genes affected

FANCC (HGNC:3584): (FA complementation group C) 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 C. [provided by RefSeq, Jul 2008]

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001243744.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 9-95111279-CAGG-C is Benign according to our data. Variant chr9-95111279-CAGG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 134307.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243744.2. 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
	FANCC	NM_000136.3	MANE Select	c.1329+181_1329+183delCCT		intron	N/A	NP_000127.2	Q00597
	FANCC	NM_001243744.2		c.1393_1395delCCT	p.Pro465del	conservative_inframe_deletion	Exon 14 of 14	NP_001230673.1	A0A087WW44
	FANCC	NM_001243743.2		c.1329+181_1329+183delCCT		intron	N/A	NP_001230672.1	A0A024R9N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000490972.7	TSL:1	c.1393_1395delCCT	p.Pro465del	conservative_inframe_deletion	Exon 14 of 14	ENSP00000479931.1	A0A087WW44
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.1329+181_1329+183delCCT		intron	N/A	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.1329+181_1329+183delCCT		intron	N/A	ENSP00000364454.1	Q00597

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000598 AC: 10 AN: 167142 AF XY: 0.0000541

Gnomad AFR exome AF: 0.000550

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: 0.0000555

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000234 AC: 33 AN: 1407410 Hom.: 0 AF XY: 0.0000158 AC XY: 11 AN XY: 697322

African (AFR) AF: 0.000651 AC: 21 AN: 32260

American (AMR) AF: 0.00 AC: 0 AN: 38128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25482

East Asian (EAS) AF: 0.00 AC: 0 AN: 36874

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000732 AC: 8 AN: 1092318

Other (OTH) AF: 0.0000509 AC: 3 AN: 58888

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74488

African (AFR) AF: 0.000577 AC: 24 AN: 41582

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000181

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	FANCC-related disorder (1)
-	-	1	Fanconi anemia complementation group C (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.034
Mutation Taster		=100/0	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: rs587778328; hg19: chr9-97873561;