NM_000136.3:c.843+87T>C

Variant names:

• chr9-95135259-A-G
• rs183585118
• NM_000136.3:c.843+87T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000136.3(FANCC):​c.843+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,314,432 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.208
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.843+87T>C		intron	N/A	NP_000127.2
	FANCC	NM_001243743.2		c.843+87T>C		intron	N/A	NP_001230672.1
	FANCC	NM_001243744.2		c.843+87T>C		intron	N/A	NP_001230673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.843+87T>C		intron	N/A	ENSP00000289081.3
	FANCC	ENST00000375305.6	TSL:1	c.843+87T>C		intron	N/A	ENSP00000364454.1
	FANCC	ENST00000490972.7	TSL:1	c.843+87T>C		intron	N/A	ENSP00000479931.1

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152202 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000379 AC: 440 AN: 1162112 Hom.: 2 AF XY: 0.000366 AC XY: 217 AN XY: 592842

African (AFR) AF: 0.00 AC: 0 AN: 27384

American (AMR) AF: 0.0000453 AC: 2 AN: 44182

Ashkenazi Jewish (ASJ) AF: 0.00462 AC: 112 AN: 24224

East Asian (EAS) AF: 0.00339 AC: 130 AN: 38300

South Asian (SAS) AF: 0.000164 AC: 13 AN: 79394

European-Finnish (FIN) AF: 0.00116 AC: 61 AN: 52656

Middle Eastern (MID) AF: 0.000267 AC: 1 AN: 3752

European-Non Finnish (NFE) AF: 0.000113 AC: 95 AN: 841776

Other (OTH) AF: 0.000515 AC: 26 AN: 50444

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152320 Hom.: 1 Cov.: 33 AF XY: 0.000389 AC XY: 29 AN XY: 74484

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

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

Alfa AF: 0.000265 Hom.: 0

Bravo AF: 0.000212

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.48
PhyloP100		-0.21
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: rs183585118; hg19: chr9-97897541;