Genetic Variant FAAP24:p.Ser126Phe (chr19-32974193-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152266.5(FAAP24):c.377C>T(p.Ser126Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00594 in 1,613,312 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 50 hom. )

Consequence

FAAP24
NM_152266.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.03

Publications

11 publications found

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]

FAAP24 Gene-Disease associations (from GenCC):

lymphoproliferative syndrome
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

FAAP24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065547526).

BP6

Variant 19-32974193-C-T is Benign according to our data. Variant chr19-32974193-C-T is described in ClinVar as Benign. ClinVar VariationId is 784831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 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.377C>T	p.Ser126Phe	missense	Exon 4 of 5	NP_689479.1	Q9BTP7
	FAAP24	NM_001300978.2		c.92C>T	p.Ser31Phe	missense	Exon 2 of 3	NP_001287907.1	K7EKQ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAAP24	ENST00000588258.6	TSL:1 MANE Select	c.377C>T	p.Ser126Phe	missense	Exon 4 of 5	ENSP00000466121.1	Q9BTP7
FAAP24	ENST00000590281.1	TSL:3	c.377C>T	p.Ser126Phe	missense	Exon 4 of 5	ENSP00000468475.1	Q9BTP7
FAAP24	ENST00000699960.1		c.377C>T	p.Ser126Phe	missense	Exon 4 of 5	ENSP00000514718.1	Q9BTP7

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

737

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00661

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00541

AC:

1353

AN:

250188

AF XY:

0.00537

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00612

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00693

Gnomad OTH exome

AF:

0.00868

GnomAD4 exome

AF:

0.00605

AC:

8842

AN:

1460976

Hom.:

Cov.:

AF XY:

0.00606

AC XY:

4405

AN XY:

726798

show subpopulations

African (AFR)

AF:

0.00182

AC:

AN:

33432

American (AMR)

AF:

0.00644

AC:

286

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

601

AN:

26100

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00208

AC:

179

AN:

86020

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00643

AC:

7144

AN:

1111784

Other (OTH)

AF:

0.00770

AC:

465

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

476

953

1429

1906

2382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00484

AC:

737

AN:

152336

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41572

American (AMR)

AF:

0.00732

AC:

112

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00661

AC:

450

AN:

68032

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00667

Hom.:

Bravo

AF:

0.00552

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00651

AC:

ExAC

AF:

0.00502

AC:

609

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00954

EpiControl

AF:

0.00895

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

FAAP24-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0066

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

7.0

Sift4G

Uncertain

0.0050

Polyphen

0.90

Vest4

0.75

MVP

0.36

MPC

0.77

ClinPred

0.032

GERP RS

4.5

Varity_R

0.53

gMVP

0.76

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over