Variant 20-3824077-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000615891.2(AP5S1):c.383C>G(p.Ala128Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

AP5S1
ENST00000615891.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

AP5S1 (HGNC:15875): (adaptor related protein complex 5 subunit sigma 1) Involved in double-strand break repair via homologous recombination and endosomal transport. Located in several cellular components, including late endosome; lysosome; and nucleoplasm. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AP5S1 links:

AP5S1 (HGNC:):

AP5S1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06941527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5S1	NM_018347.3 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3	ENST00000615891.2	NP_060817.1	Q9NUS5
AP5S1	NM_001204446.2 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3		NP_001191375.1	Q9NUS5
AP5S1	NM_001204447.2 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3		NP_001191376.1	Q9NUS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AP5S1	ENST00000615891.2 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3	1	NM_018347.3	ENSP00000481750.1	Q9NUS5
AP5S1	ENST00000379573.6 linkuse as main transcript	c.*199C>G		3_prime_UTR_variant	3/3	1		ENSP00000368892.2	Q5JX74
AP5S1	ENST00000246041.6 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3	4			Q9NUS5
AP5S1	ENST00000379567.6 linkuse as main transcript	c.383C>G	p.Ala128Gly	missense_variant	3/3	2		ENSP00000368886.2	Q9NUS5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250376

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461540

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000624

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 17, 2021

The c.383C>G (p.A128G) alteration is located in exon 3 (coding exon 2) of the AP5S1 gene. This alteration results from a C to G substitution at nucleotide position 383, causing the alanine (A) at amino acid position 128 to be replaced by a glycine (G). 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

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

T;.;.

M_CAP

Benign

0.0054

MetaRNN

Benign

0.069

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.032

Sift

Benign

0.066

T;T;.

Sift4G

Benign

0.074

T;T;T

Polyphen

0.039

B;B;B

Vest4

0.13

MutPred

0.33

Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);

MVP

0.11

MPC

0.064

ClinPred

0.34

GERP RS

4.8

Varity_R

0.10

gMVP

0.17

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.

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