19-32973239-C-G

Variant names:

• chr19-32973239-C-G
• NM_152266.5:c.43C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152266.5(FAAP24):​c.43C>G​(p.Pro15Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P15T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAAP24 NM_152266.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61
• Publications: 0 publications found

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]

FAAP24 Gene-Disease associations (from GenCC):

• lymphoproliferative syndrome

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152266.5. 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
	FAAP24	NM_152266.5	MANE Select	c.43C>G	p.Pro15Ala	missense	Exon 2 of 5	NP_689479.1	Q9BTP7
	FAAP24	NM_001300978.2		c.-42-821C>G		intron	N/A	NP_001287907.1	K7EKQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAP24	ENST00000588258.6	TSL:1 MANE Select	c.43C>G	p.Pro15Ala	missense	Exon 2 of 5	ENSP00000466121.1	Q9BTP7
	FAAP24	ENST00000590281.1	TSL:3	c.43C>G	p.Pro15Ala	missense	Exon 2 of 5	ENSP00000468475.1	Q9BTP7
	FAAP24	ENST00000699960.1		c.43C>G	p.Pro15Ala	missense	Exon 2 of 5	ENSP00000514718.1	Q9BTP7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.6
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.70
MutPred		0.73		Loss of sheet (P = 3e-04)
MVP		0.39
MPC		0.97
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.59
gMVP		0.69
Mutation Taster		=34/66	disease causing

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

Other links and lift over

hg19: chr19-33464145;