19-32973239-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152266.5(FAAP24):​c.43C>A​(p.Pro15Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,842 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAAP24
NM_152266.5 missense

Scores

4
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61
Variant links:
Genes affected
FAAP24 (HGNC:28467): (FA core complex associated protein 24) FAAP24 is a component of the Fanconi anemia (FA) core complex (see MIM 227650), which plays a crucial role in DNA damage response (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAAP24NM_152266.5 linkc.43C>A p.Pro15Thr missense_variant Exon 2 of 5 ENST00000588258.6 NP_689479.1 Q9BTP7A0A0S2Z5V6
FAAP24XM_005259393.4 linkc.-29C>A 5_prime_UTR_variant Exon 2 of 5 XP_005259450.1
FAAP24NM_001300978.2 linkc.-42-821C>A intron_variant Intron 1 of 2 NP_001287907.1 Q9BTP7K7EKQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAAP24ENST00000588258.6 linkc.43C>A p.Pro15Thr missense_variant Exon 2 of 5 1 NM_152266.5 ENSP00000466121.1 Q9BTP7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251482
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135916
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:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461842
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 16, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>A (p.P15T) alteration is located in exon 2 (coding exon 1) of the FAAP24 gene. This alteration results from a C to A substitution at nucleotide position 43, causing the proline (P) at amino acid position 15 to be replaced by a threonine (T). 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
Uncertain
0.40
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.80
.;T
M_CAP
Benign
0.071
D
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Uncertain
2.7
M;M
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.97
D;D
Vest4
0.78
MutPred
0.75
Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);
MVP
0.39
MPC
1.0
ClinPred
0.92
D
GERP RS
4.5
Varity_R
0.79
gMVP
0.76

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: rs1230523746; hg19: chr19-33464145; API