Genetic Variant FAAP20:p.Ala142Pro (chr1-2193685-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182533.4(FAAP20):c.424G>C(p.Ala142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A142G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FAAP20
NM_182533.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039004475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAAP20	NM_182533.4	MANE Select	c.424G>C	p.Ala142Pro	missense	Exon 3 of 4	NP_872339.3	Q6NZ36-1
FAAP20	NM_001282670.2		c.733G>C	p.Ala245Pro	missense	Exon 7 of 8	NP_001269599.1	Q6NZ36-2
FAAP20	NM_001256946.2		c.424G>C	p.Ala142Pro	missense	Exon 3 of 4	NP_001243875.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAAP20	ENST00000378546.9	TSL:1 MANE Select	c.424G>C	p.Ala142Pro	missense	Exon 3 of 4	ENSP00000367808.4	Q6NZ36-1
FAAP20	ENST00000420515.1	TSL:1	c.421G>C	p.Ala141Pro	missense	Exon 3 of 4	ENSP00000409721.1	H7C361
FAAP20	ENST00000401813.7	TSL:1	n.2263G>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.23

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.33

M_CAP

Benign

0.012

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

-0.023

PROVEAN

Benign

-0.010

REVEL

Benign

0.010

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.11

MutPred

0.14

Gain of glycosylation at A142 (P = 0.0668)

MVP

0.17

MPC

0.56

ClinPred

0.039

GERP RS

-5.9

Varity_R

0.44

Mutation Taster

=299/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over