chr19-32974100-G-A

Variant names:

• chr19-32974100-G-A
• rs78628256
• NM_152266.5:c.284G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152266.5(FAAP24):​c.284G>A​(p.Arg95Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000541 in 1,614,094 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: FAAP24 NM_152266.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.607
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043139756).
• BP6: Variant 19-32974100-G-A is Benign according to our data. Variant chr19-32974100-G-A is described in ClinVar as Benign. ClinVar VariationId is 714784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.284G>A	p.Arg95Gln	missense	Exon 4 of 5	NP_689479.1	Q9BTP7
	FAAP24	NM_001300978.2		c.-2G>A		5_prime_UTR	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.284G>A	p.Arg95Gln	missense	Exon 4 of 5	ENSP00000466121.1	Q9BTP7
	FAAP24	ENST00000590281.1	TSL:3	c.284G>A	p.Arg95Gln	missense	Exon 4 of 5	ENSP00000468475.1	Q9BTP7
	FAAP24	ENST00000699960.1		c.284G>A	p.Arg95Gln	missense	Exon 4 of 5	ENSP00000514718.1	Q9BTP7

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 469 AN: 152134 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000835 AC: 210 AN: 251384 AF XY: 0.000640

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000276 AC: 404 AN: 1461842 Hom.: 2 Cov.: 31 AF XY: 0.000234 AC XY: 170 AN XY: 727214

African (AFR) AF: 0.00938 AC: 314 AN: 33478

American (AMR) AF: 0.00101 AC: 45 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1111996

Other (OTH) AF: 0.000480 AC: 29 AN: 60394

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152252 Hom.: 2 Cov.: 33 AF XY: 0.00275 AC XY: 205 AN XY: 74434

African (AFR) AF: 0.0100 AC: 417 AN: 41544

American (AMR) AF: 0.00334 AC: 51 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000939 Hom.: 1

Bravo AF: 0.00312

ESP6500AA AF: 0.0104 AC: 46

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00105 AC: 127

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FAAP24-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.90
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.61
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.055
MPC		0.33
ClinPred		0.00082	T
GERP RS		-1.4
Varity_R		0.087
gMVP		0.12
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs78628256; hg19: chr19-33465006;