9-95099155-A-G

Variant names:

• chr9-95099155-A-G
• rs9673
• NM_000136.3:c.*2552T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000136.3(FANCC):​c.*2552T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 215,522 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (84 hom., cov: 31)
  • Exomes 𝑓: 0.023 (23 hom.)
• Consequence: FANCC NM_000136.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 9-95099155-A-G is Benign according to our data. Variant chr9-95099155-A-G is described in ClinVar as Benign. ClinVar VariationId is 367569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0272 (4138/152310) while in subpopulation AMR AF = 0.0433 (662/15306). AF 95% confidence interval is 0.0405. There are 84 homozygotes in GnomAd4. There are 2057 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 84 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.*2552T>C		3_prime_UTR	Exon 15 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.*2552T>C		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.*2552T>C		3_prime_UTR	Exon 15 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.*2552T>C		3_prime_UTR	Exon 15 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000919082.1		c.*2552T>C		3_prime_UTR	Exon 15 of 15	ENSP00000589141.1

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4138 AN: 152192 Hom.: 84 Cov.: 31

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0231 AC: 1463 AN: 63212 Hom.: 23 Cov.: 0 AF XY: 0.0233 AC XY: 682 AN XY: 29312

African (AFR) AF: 0.00495 AC: 14 AN: 2828

American (AMR) AF: 0.0486 AC: 87 AN: 1790

Ashkenazi Jewish (ASJ) AF: 0.00939 AC: 38 AN: 4048

East Asian (EAS) AF: 0.00 AC: 0 AN: 9308

South Asian (SAS) AF: 0.0148 AC: 8 AN: 540

European-Finnish (FIN) AF: 0.0370 AC: 2 AN: 54

Middle Eastern (MID) AF: 0.00761 AC: 3 AN: 394

European-Non Finnish (NFE) AF: 0.0305 AC: 1189 AN: 38972

Other (OTH) AF: 0.0231 AC: 122 AN: 5278

GnomAD4 genome AF: 0.0272 AC: 4138 AN: 152310 Hom.: 84 Cov.: 31 AF XY: 0.0276 AC XY: 2057 AN XY: 74482

African (AFR) AF: 0.00642 AC: 267 AN: 41578

American (AMR) AF: 0.0433 AC: 662 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4822

European-Finnish (FIN) AF: 0.0544 AC: 577 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2430 AN: 68024

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0302 Hom.: 103

Bravo AF: 0.0248

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-1.0
CADD	Benign	0.087
DANN	Benign	0.28
PhyloP100		-1.2
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: rs9673; hg19: chr9-97861437;