X-15845830-A-T

Position:

• chrX-15845830-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001272071.2(AP1S2):​c.288+73T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (38564 hom., 32602 hem., cov: 22)
  • Exomes 𝑓: 0.99 (285810 hom. 239252 hem.)
  • Failed GnomAD Quality Control
• Consequence: AP1S2 NM_001272071.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant X-15845830-A-T is Benign according to our data. Variant chrX-15845830-A-T is described in ClinVar as [Benign]. Clinvar id is 1276725.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP1S2	NM_001272071.2	c.288+73T>A		intron_variant		ENST00000672987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP1S2	ENST00000672987.1	c.288+73T>A		intron_variant			NM_001272071.2	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 110037 AN: 110518 Hom.: 38568 Cov.: 22 AF XY: 0.996 AC XY: 32545 AN XY: 32662 FAILED QC

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.995

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.999

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.993 AC: 814890 AN: 820361 Hom.: 285810 AF XY: 0.994 AC XY: 239252 AN XY: 240667

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 0.992

Gnomad4 OTH exome AF: 0.994

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.996 AC: 110085 AN: 110566 Hom.: 38564 Cov.: 22 AF XY: 0.996 AC XY: 32602 AN XY: 32720

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.999

Alfa AF: 0.995 Hom.: 9223

Bravo AF: 0.997

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	-0.68
CADD	Benign	7.3
DANN	Benign	0.67

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: rs798169; hg19: chrX-15863953;