X-15845153-T-C

Position:

• chrX-15845153-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001272071.2(AP1S2):​c.426+226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 751,502 control chromosomes in the GnomAD database, including 16,114 homozygotes. There are 55,479 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (2360 hom., 7905 hem., cov: 22)
  • Exomes 𝑓: 0.25 (13754 hom. 47574 hem.)
• Consequence: AP1S2 NM_001272071.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-15845153-T-C is Benign according to our data. Variant chrX-15845153-T-C is described in ClinVar as [Benign]. Clinvar id is 1264730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP1S2	NM_001272071.2	c.426+226A>G		intron_variant		ENST00000672987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP1S2	ENST00000672987.1	c.426+226A>G		intron_variant			NM_001272071.2	P3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 26829 AN: 111032 Hom.: 2362 Cov.: 22 AF XY: 0.237 AC XY: 7892 AN XY: 33238

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.247 AC: 158488 AN: 640418 Hom.: 13754 Cov.: 24 AF XY: 0.248 AC XY: 47574 AN XY: 192074

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.242 AC: 26846 AN: 111084 Hom.: 2360 Cov.: 22 AF XY: 0.237 AC XY: 7905 AN XY: 33300

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.282

Alfa AF: 0.118 Hom.: 579

Bravo AF: 0.257

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs3788929; hg19: chrX-15863276;