Variant chr19-49799456-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_130787.3(AP2A1):c.1095C>T(p.Ala365Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,611,686 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 63 hom. )

Consequence

AP2A1
NM_130787.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

AP2A1 (HGNC:561): (adaptor related protein complex 2 subunit alpha 1) This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles. Alternative splicing of this gene results in two transcript variants encoding two different isoforms. A third transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

AP2A1 links:

LOC124904742 (HGNC:):

LOC124904742 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 19-49799456-C-T is Benign according to our data. Variant chr19-49799456-C-T is described in ClinVar as [Benign]. Clinvar id is 782059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00376 (5490/1459410) while in subpopulation MID AF= 0.0262 (151/5764). AF 95% confidence interval is 0.0228. There are 63 homozygotes in gnomad4_exome. There are 3077 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 457 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2A1	NM_130787.3 linkuse as main transcript	c.1095C>T	p.Ala365Ala	synonymous_variant	9/23	ENST00000354293.10	NP_570603.2	O95782-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AP2A1	ENST00000354293.10 linkuse as main transcript	c.1095C>T	p.Ala365Ala	synonymous_variant	9/23	1	NM_130787.3	ENSP00000346246.4	O95782-2
AP2A1	ENST00000359032.10 linkuse as main transcript	c.1095C>T	p.Ala365Ala	synonymous_variant	9/24	5		ENSP00000351926.4	O95782-1
AP2A1	ENST00000597774.5 linkuse as main transcript	n.*433C>T		non_coding_transcript_exon_variant	7/22	5		ENSP00000472492.1	M0R2D9
AP2A1	ENST00000597774.5 linkuse as main transcript	n.*433C>T		3_prime_UTR_variant	7/22	5		ENSP00000472492.1	M0R2D9

Frequencies

GnomAD3 genomes

AF:

0.00298

AC:

453

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00521

AC:

1275

AN:

244692

Hom.:

AF XY:

0.00559

AC XY:

744

AN XY:

133148

show subpopulations

Gnomad AFR exome

AF:

0.000807

Gnomad AMR exome

AF:

0.00473

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00324

Gnomad OTH exome

AF:

0.00836

GnomAD4 exome

AF:

0.00376

AC:

5490

AN:

1459410

Hom.:

Cov.:

AF XY:

0.00424

AC XY:

3077

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00477

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0000574

Gnomad4 NFE exome

AF:

0.00253

Gnomad4 OTH exome

AF:

0.00641

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152276

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00257

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00404

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.66

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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