9-95099543-C-T

Variant names:

• chr9-95099543-C-T
• rs566582636
• NM_000136.3:c.*2164G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000136.3(FANCC):​c.*2164G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000643 in 230,274 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: FANCC NM_000136.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-95099543-C-T is Benign according to our data. Variant chr9-95099543-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 913943.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00155 (122/78490) while in subpopulation EAS AF = 0.0106 (118/11152). AF 95% confidence interval is 0.00903. There are 0 homozygotes in GnomAdExome4. There are 55 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.*2164G>A		3_prime_UTR	Exon 15 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.*2164G>A		3_prime_UTR	Exon 15 of 15	NP_001230672.1	A0A024R9N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.*2164G>A		3_prime_UTR	Exon 15 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.*2164G>A		3_prime_UTR	Exon 15 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000919082.1		c.*2164G>A		3_prime_UTR	Exon 15 of 15	ENSP00000589141.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151666 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000969

Gnomad SAS AF: 0.00336

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00155 AC: 122 AN: 78490 Hom.: 0 Cov.: 0 AF XY: 0.00152 AC XY: 55 AN XY: 36134

African (AFR) AF: 0.00 AC: 0 AN: 3720

American (AMR) AF: 0.00 AC: 0 AN: 2396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4964

East Asian (EAS) AF: 0.0106 AC: 118 AN: 11152

South Asian (SAS) AF: 0.00576 AC: 4 AN: 694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 66

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 480

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48474

Other (OTH) AF: 0.00 AC: 0 AN: 6544

GnomAD4 genome AF: 0.000171 AC: 26 AN: 151784 Hom.: 0 Cov.: 31 AF XY: 0.000243 AC XY: 18 AN XY: 74154

African (AFR) AF: 0.00 AC: 0 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000971 AC: 5 AN: 5148

South Asian (SAS) AF: 0.00336 AC: 16 AN: 4756

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Fanconi anemia complementation group C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-0.19
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: rs566582636; hg19: chr9-97861825;