19-32974193-C-T

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0061 ( 50 hom. )

Consequence

FAAP24
NM_152266.5 missense

Scores

2
5
7

Clinical Significance

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

Conservation

PhyloP100: 7.03
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 Benign. Variant got -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 id is 784831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-32974193-C-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAAP24NM_152266.5 linkc.377C>T p.Ser126Phe missense_variant Exon 4 of 5 ENST00000588258.6 NP_689479.1 Q9BTP7A0A0S2Z5V6
FAAP24NM_001300978.2 linkc.92C>T p.Ser31Phe missense_variant Exon 2 of 3 NP_001287907.1 Q9BTP7K7EKQ4
FAAP24XM_005259393.4 linkc.248C>T p.Ser83Phe missense_variant Exon 4 of 5 XP_005259450.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAAP24ENST00000588258.6 linkc.377C>T p.Ser126Phe missense_variant Exon 4 of 5 1 NM_152266.5 ENSP00000466121.1 Q9BTP7

Frequencies

GnomAD3 genomes
AF:
0.00484
AC:
737
AN:
152218
Hom.:
4
Cov.:
33
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
GnomAD3 exomes
AF:
0.00541
AC:
1353
AN:
250188
Hom.:
12
AF XY:
0.00537
AC XY:
727
AN XY:
135278
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 SAS exome
AF:
0.00201
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.:
50
Cov.:
31
AF XY:
0.00606
AC XY:
4405
AN XY:
726798
show subpopulations
Gnomad4 AFR exome
AF:
0.00182
Gnomad4 AMR exome
AF:
0.00644
Gnomad4 ASJ exome
AF:
0.0230
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00208
Gnomad4 FIN exome
AF:
0.000300
Gnomad4 NFE exome
AF:
0.00643
Gnomad4 OTH exome
AF:
0.00770
GnomAD4 genome
AF:
0.00484
AC:
737
AN:
152336
Hom.:
4
Cov.:
33
AF XY:
0.00448
AC XY:
334
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.00732
Gnomad4 ASJ
AF:
0.0207
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00661
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.00713
Hom.:
10
Bravo
AF:
0.00552
TwinsUK
AF:
0.00512
AC:
19
ALSPAC
AF:
0.00597
AC:
23
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00651
AC:
56
ExAC
AF:
0.00502
AC:
609
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.00954
EpiControl
AF:
0.00895

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

FAAP24-related disorder Benign:1
Feb 24, 2020
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.69
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.40
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
.;T;.;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.86
.;.;D;D
MetaRNN
Benign
0.0066
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
.;M;.;M
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
0.90
.;P;.;P
Vest4
0.75
MVP
0.36
MPC
0.77
ClinPred
0.032
T
GERP RS
4.5
Varity_R
0.53
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: rs36017455; hg19: chr19-33465099; COSMIC: COSV99039011; COSMIC: COSV99039011; API