9-95107106-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000136.3(FANCC):​c.1493C>G​(p.Ala498Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A498V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

FANCC
NM_000136.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.23
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3098029).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FANCCNM_000136.3 linkuse as main transcriptc.1493C>G p.Ala498Gly missense_variant 14/15 ENST00000289081.8
LOC107987102XR_001746847.2 linkuse as main transcriptn.524G>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FANCCENST00000289081.8 linkuse as main transcriptc.1493C>G p.Ala498Gly missense_variant 14/151 NM_000136.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;T
Eigen
Benign
-0.096
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.73
.;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.11
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.034
D;D
Polyphen
0.82
P;P
Vest4
0.20
MutPred
0.44
Loss of stability (P = 0.0387);Loss of stability (P = 0.0387);
MVP
0.76
MPC
0.27
ClinPred
0.65
D
GERP RS
3.1
Varity_R
0.10
gMVP
0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-97869388; API