NM_000136.3:c.*1895T>C

Variant names:

• chr9-95099812-A-G
• rs56161090
• NM_000136.3:c.*1895T>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.*1895T>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 0.00336 in 232,456 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: FANCC NM_000136.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.433
• Publications: 2 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=-0.9).
• BP6: Variant 9-95099812-A-G is Benign according to our data. Variant chr9-95099812-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 367579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00454 (692/152332) while in subpopulation AFR AF = 0.0159 (663/41572). AF 95% confidence interval is 0.0149. There are 3 homozygotes in GnomAd4. There are 355 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.*1895T>C		3_prime_UTR	Exon 15 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.*1895T>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.*1895T>C		3_prime_UTR	Exon 15 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.*1895T>C		3_prime_UTR	Exon 15 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000919082.1		c.*1895T>C		3_prime_UTR	Exon 15 of 15	ENSP00000589141.1

Frequencies

GnomAD3 genomes AF: 0.00455 AC: 692 AN: 152214 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00112 AC: 90 AN: 80124 Hom.: 0 Cov.: 0 AF XY: 0.00103 AC XY: 38 AN XY: 37006

African (AFR) AF: 0.0180 AC: 69 AN: 3840

American (AMR) AF: 0.00122 AC: 3 AN: 2462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5064

East Asian (EAS) AF: 0.00 AC: 0 AN: 11262

South Asian (SAS) AF: 0.00 AC: 0 AN: 698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 82

Middle Eastern (MID) AF: 0.00203 AC: 1 AN: 492

European-Non Finnish (NFE) AF: 0.000101 AC: 5 AN: 49528

Other (OTH) AF: 0.00179 AC: 12 AN: 6696

GnomAD4 genome AF: 0.00454 AC: 692 AN: 152332 Hom.: 3 Cov.: 31 AF XY: 0.00477 AC XY: 355 AN XY: 74488

African (AFR) AF: 0.0159 AC: 663 AN: 41572

American (AMR) AF: 0.00111 AC: 17 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00313 Hom.: 1

Bravo AF: 0.00518

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	1.8
DANN	Benign	0.33
PhyloP100		0.43

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: rs56161090; hg19: chr9-97862094;