9-35078731-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004629.2(FANCG):c.181C>T(p.Pro61Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
FANCG
NM_004629.2 missense
NM_004629.2 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 5.33
Genes affected
FANCG (HGNC:3588): (FA complementation group G) 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 G. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.822
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCG | NM_004629.2 | c.181C>T | p.Pro61Ser | missense_variant | 3/14 | ENST00000378643.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCG | ENST00000378643.8 | c.181C>T | p.Pro61Ser | missense_variant | 3/14 | 1 | NM_004629.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152120Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
152120
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD3 exomes
AF:
AC:
2
AN:
251408
Hom.:
AF XY:
AC XY:
1
AN XY:
135894
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 exome
AF:
AC:
5
AN:
1461860
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727236
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74292
GnomAD4 genome
?
AF:
AC:
5
AN:
152120
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74292
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fanconi anemia complementation group G Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 29, 2021 | - - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 61 of the FANCG protein (p.Pro61Ser). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with fanconi anemia (PMID: 32947577). ClinVar contains an entry for this variant (Variation ID: 569286). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCG protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at