17-81547121-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025161.6(FAAP100):​c.1961G>A​(p.Arg654His) variant causes a missense change. The variant allele was found at a frequency of 0.0000085 in 1,528,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R654C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

FAAP100
NM_025161.6 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02
Variant links:
Genes affected
FAAP100 (HGNC:26171): (FA core complex associated protein 100) FAAP100 is a component of the Fanconi anemia (FA; MIM 277650) core complex and is required for core complex stability and FANCD2 (see MIM 227646) monoubiquitination (Ling et al., 2007 [PubMed 17396147]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAAP100NM_025161.6 linkc.1961G>A p.Arg654His missense_variant Exon 5 of 9 ENST00000327787.13 NP_079437.5 Q0VG06-1A4ZI32

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAAP100ENST00000327787.13 linkc.1961G>A p.Arg654His missense_variant Exon 5 of 9 1 NM_025161.6 ENSP00000333283.8 Q0VG06-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151972
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000541
AC:
1
AN:
184916
Hom.:
0
AF XY:
0.0000101
AC XY:
1
AN XY:
98922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000117
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000508
AC:
7
AN:
1376708
Hom.:
0
Cov.:
36
AF XY:
0.00000592
AC XY:
4
AN XY:
675782
show subpopulations
Gnomad4 AFR exome
AF:
0.0000325
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000135
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000468
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151972
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.00000833
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1961G>A (p.R654H) alteration is located in exon 5 (coding exon 5) of the FAAP100 gene. This alteration results from a G to A substitution at nucleotide position 1961, causing the arginine (R) at amino acid position 654 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Benign
-0.42
T
MutationAssessor
Uncertain
2.7
M;.
PROVEAN
Uncertain
-3.3
D;D
REVEL
Benign
0.19
Sift
Uncertain
0.022
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.48
MVP
0.67
MPC
1.2
ClinPred
0.94
D
GERP RS
3.9
Varity_R
0.14
gMVP
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764783034; hg19: chr17-79514147; API