Variant X-15845525-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001272071.2(AP1S2):c.289-10_289-9insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,062,827 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 12 hem., cov: 22)

Exomes 𝑓: 0.00058 ( 0 hom. 35 hem. )

Consequence

AP1S2
NM_001272071.2 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

AP1S2 (HGNC:560): (adaptor related protein complex 1 subunit sigma 2) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as the small subunit of this complex and is a member of the adaptin protein family. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

AP1S2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-15845525-G-GA is Benign according to our data. Variant chrX-15845525-G-GA is described in ClinVar as [Benign]. Clinvar id is 2039329.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP1S2	NM_001272071.2 linkuse as main transcript	c.289-10_289-9insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000672987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP1S2	ENST00000672987.1 linkuse as main transcript	c.289-10_289-9insT		splice_polypyrimidine_tract_variant, intron_variant			NM_001272071.2	P3

Frequencies

GnomAD3 genomes

AF:

0.000241

AC:

AN:

99649

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

AN XY:

27123

show subpopulations

Gnomad AFR

AF:

0.000110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000304

Gnomad SAS

AF:

0.00556

Gnomad FIN

AF:

0.000236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000124

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00129

AC:

145

AN:

112281

Hom.:

AF XY:

0.000218

AC XY:

AN XY:

36773

show subpopulations

Gnomad AFR exome

AF:

0.000242

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00112

Gnomad EAS exome

AF:

0.00101

Gnomad SAS exome

AF:

0.00422

Gnomad FIN exome

AF:

0.000331

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000768

GnomAD4 exome

AF:

0.000579

AC:

558

AN:

963163

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

303189

show subpopulations

Gnomad4 AFR exome

AF:

0.000550

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.000435

Gnomad4 EAS exome

AF:

0.000464

Gnomad4 SAS exome

AF:

0.00352

Gnomad4 FIN exome

AF:

0.000416

Gnomad4 NFE exome

AF:

0.000396

Gnomad4 OTH exome

AF:

0.000627

GnomAD4 genome

AF:

0.000241

AC:

AN:

99664

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

AN XY:

27156

show subpopulations

Gnomad4 AFR

AF:

0.000110

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000305

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.000236

Gnomad4 NFE

AF:

0.000124

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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