rs55719336

Variant names:

• chr9-95135373-G-A
• rs55719336
• NM_000136.3:c.816C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-95135373-G-A
• chr9-95135373-G-C
• chr9-95135373-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000136.3(FANCC):​c.816C>T​(p.Ile272Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,613,888 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I272I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00094 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (7 hom.)
• Consequence: FANCC NM_000136.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:12
• Conservation: PhyloP100: -0.472
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 9-95135373-G-A is Benign according to our data. Variant chr9-95135373-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.472 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00094 (143/152148) while in subpopulation EAS AF = 0.0131 (68/5178). AF 95% confidence interval is 0.0106. There are 2 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	NM_000136.3	MANE Select	c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 15	NP_001230672.1	A0A024R9N2
	FANCC	NM_001243744.2		c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 14	NP_001230673.1	A0A087WW44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000490972.7	TSL:1	c.816C>T	p.Ile272Ile	synonymous	Exon 8 of 14	ENSP00000479931.1	A0A087WW44

Frequencies

GnomAD3 genomes AF: 0.000941 AC: 143 AN: 152030 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00130 AC: 326 AN: 251432 AF XY: 0.00119

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000350 AC: 512 AN: 1461740 Hom.: 7 Cov.: 31 AF XY: 0.000369 AC XY: 268 AN XY: 727162

African (AFR) AF: 0.000657 AC: 22 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00733 AC: 291 AN: 39692

South Asian (SAS) AF: 0.000858 AC: 74 AN: 86236

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111956

Other (OTH) AF: 0.00141 AC: 85 AN: 60392

GnomAD4 genome AF: 0.000940 AC: 143 AN: 152148 Hom.: 2 Cov.: 33 AF XY: 0.000995 AC XY: 74 AN XY: 74368

African (AFR) AF: 0.00128 AC: 53 AN: 41498

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5178

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000185 Hom.: 0

Bravo AF: 0.000979

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	1	2	not provided (3)
-	-	2	Fanconi anemia (2)
-	-	1	FANCC-related disorder (1)
-	-	1	Fanconi anemia complementation group C (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.0
DANN	Benign	0.79
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55719336; hg19: chr9-97897655;