chr19-32974208-A-C

Variant names:

• chr19-32974208-A-C
• rs1352538271
• NM_152266.5:c.392A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152266.5(FAAP24):​c.392A>C​(p.Gln131Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,588 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAAP24 NM_152266.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.48
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

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.392A>C	p.Gln131Pro	missense	Exon 4 of 5	NP_689479.1	Q9BTP7
	FAAP24	NM_001300978.2		c.107A>C	p.Gln36Pro	missense	Exon 2 of 3	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.392A>C	p.Gln131Pro	missense	Exon 4 of 5	ENSP00000466121.1	Q9BTP7
	FAAP24	ENST00000590281.1	TSL:3	c.392A>C	p.Gln131Pro	missense	Exon 4 of 5	ENSP00000468475.1	Q9BTP7
	FAAP24	ENST00000699960.1		c.392A>C	p.Gln131Pro	missense	Exon 4 of 5	ENSP00000514718.1	Q9BTP7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460588 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726594

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.0000226 AC: 1 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.5
Sift4G	Uncertain	0.013	D
Polyphen		0.96	P
Vest4		0.85
MutPred		0.45		Gain of disorder (P = 0.1828)
MVP		0.30
MPC		0.58
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.93
gMVP		0.84
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs1352538271; hg19: chr19-33465114;