Variant chr1-2193680-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_182533.4(FAAP20):c.429C>G(p.Ala143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,600,546 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAAP20
NM_182533.4 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.549

Variant links:

Genes affected

FAAP20 (HGNC:26428): (FA core complex associated protein 20) Enables K63-linked polyubiquitin modification-dependent protein binding activity and ubiquitin-dependent protein binding activity. Involved in interstrand cross-link repair and translesion synthesis. Located in cell junction; chromosome; and nuclear body. Part of Fanconi anaemia nuclear complex. [provided by Alliance of Genome Resources, Apr 2022]

FAAP20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053045988).

BP7

Synonymous conserved (PhyloP=-0.549 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAP20	NM_182533.4 linkuse as main transcript	c.429C>G	p.Ala143=	synonymous_variant	3/4	ENST00000378546.9	NP_872339.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAP20	ENST00000378546.9 linkuse as main transcript	c.429C>G	p.Ala143=	synonymous_variant	3/4	1	NM_182533.4	ENSP00000367808	P1	Q6NZ36-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000655

AC:

AN:

228956

Hom.:

AF XY:

0.0000473

AC XY:

AN XY:

126852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000663

Gnomad SAS exome

AF:

0.0000342

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000538

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1448418

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

720792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000301

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000962

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000754

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.416C>G (p.P139R) alteration is located in exon 7 (coding exon 3) of the FAAP20 gene. This alteration results from a C to G substitution at nucleotide position 416, causing the proline (P) at amino acid position 139 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.5

DANN

Benign

0.57

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.15

Sift4G

Pathogenic

0.0

D;T

Vest4

0.22

MVP

0.18

ClinPred

0.20

GERP RS

-1.5

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.2

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over