Genetic Variant FAAP20:p.Ala142Thr (chr1-2193685-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_182533.4(FAAP20):c.424G>A(p.Ala142Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,447,164 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. Variant has been reported in ClinVar as Likely benign (★). 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: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FAAP20
NM_182533.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029695839).

BP6

Variant 1-2193685-C-T is Benign according to our data. Variant chr1-2193685-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3511368.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Ala142Thr	missense	Exon 3 of 4	NP_872339.3	Q6NZ36-1
FAAP20	NM_001282670.2		c.733G>A	p.Ala245Thr	missense	Exon 7 of 8	NP_001269599.1	Q6NZ36-2
FAAP20	NM_001256946.2		c.424G>A	p.Ala142Thr	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>A	p.Ala142Thr	missense	Exon 3 of 4	ENSP00000367808.4	Q6NZ36-1
FAAP20	ENST00000420515.1	TSL:1	c.421G>A	p.Ala141Thr	missense	Exon 3 of 4	ENSP00000409721.1	H7C361
FAAP20	ENST00000401813.7	TSL:1	n.2263G>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000615

AC:

AN:

227568

AF XY:

0.0000555

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000467

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000207

AC:

AN:

1447164

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

720188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32468

American (AMR)

AF:

0.000500

AC:

AN:

40010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25436

East Asian (EAS)

AF:

0.00

AC:

AN:

39552

South Asian (SAS)

AF:

0.00

AC:

AN:

84914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00000813

AC:

AN:

1107680

Other (OTH)

AF:

0.0000167

AC:

AN:

59732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000838

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.5

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.35

M_CAP

Benign

0.010

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

-0.023

PROVEAN

Benign

-0.10

REVEL

Benign

0.0080

Sift

Benign

0.44

Sift4G

Benign

0.50

Polyphen

0.0010

Vest4

0.078

MutPred

0.11

Gain of phosphorylation at A142 (P = 0.0337)

MVP

0.25

MPC

0.26

ClinPred

0.025

GERP RS

-5.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.2

Varity_R

0.10

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

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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