rs694353

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_007166.4(PICALM):c.1770T>G(p.Ala590Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,539,134 control chromosomes in the GnomAD database, including 266,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A590A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.59 ( 26907 hom., cov: 33)

Exomes 𝑓: 0.58 ( 239128 hom. )

Consequence

PICALM
NM_007166.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.37

Publications

18 publications found

Variant links:

Genes affected

PICALM (HGNC:15514): (phosphatidylinositol binding clathrin assembly protein) This gene encodes a clathrin assembly protein, which recruits clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. The protein may be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. The protein is involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. A chromosomal translocation t(10;11)(p13;q14) leading to the fusion of this gene and the MLLT10 gene is found in acute lymphoblastic leukemia, acute myeloid leukemia and malignant lymphomas. The polymorphisms of this gene are associated with the risk of Alzheimer disease. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

PICALM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.034).

BP6

Variant 11-85981138-A-C is Benign according to our data. Variant chr11-85981138-A-C is described in ClinVar as Benign. ClinVar VariationId is 403297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICALM	NM_007166.4 link	c.1770T>G	p.Ala590Ala	synonymous_variant	Exon 17 of 20	ENST00000393346.8	NP_009097.2	Q13492-1A0A024R5P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICALM	ENST00000393346.8 link	c.1770T>G	p.Ala590Ala	synonymous_variant	Exon 17 of 20	1	NM_007166.4	ENSP00000377015.3		Q13492-1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90083

AN:

151998

Hom.:

26886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.565

GnomAD2 exomes

AF:

0.597

AC:

149489

AN:

250604

AF XY:

0.597

show subpopulations

Gnomad AFR exome

AF:

0.613

Gnomad AMR exome

AF:

0.644

Gnomad ASJ exome

AF:

0.491

Gnomad EAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.599

GnomAD4 exome

AF:

0.584

AC:

810694

AN:

1387018

Hom.:

239128

Cov.:

AF XY:

0.587

AC XY:

407591

AN XY:

694432

show subpopulations

African (AFR)

AF:

0.615

AC:

19527

AN:

31748

American (AMR)

AF:

0.638

AC:

28329

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

12636

AN:

25682

East Asian (EAS)

AF:

0.667

AC:

26180

AN:

39268

South Asian (SAS)

AF:

0.650

AC:

54871

AN:

84466

European-Finnish (FIN)

AF:

0.510

AC:

27219

AN:

53320

Middle Eastern (MID)

AF:

0.555

AC:

3117

AN:

5612

European-Non Finnish (NFE)

AF:

0.579

AC:

604717

AN:

1044662

Other (OTH)

AF:

0.589

AC:

34098

AN:

57856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13364

26728

40093

53457

66821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16322

32644

48966

65288

81610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.593

AC:

90155

AN:

152116

Hom.:

26907

Cov.:

AF XY:

0.588

AC XY:

43744

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.611

AC:

25356

AN:

41474

American (AMR)

AF:

0.623

AC:

9527

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1705

AN:

3466

East Asian (EAS)

AF:

0.660

AC:

3416

AN:

5178

South Asian (SAS)

AF:

0.663

AC:

3198

AN:

4824

European-Finnish (FIN)

AF:

0.488

AC:

5171

AN:

10588

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.588

AC:

39985

AN:

67974

Other (OTH)

AF:

0.566

AC:

1196

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1931

3863

5794

7726

9657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.574

Hom.:

13934

Bravo

AF:

0.599

EpiCase

AF:

0.585

EpiControl

AF:

0.580

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

PICALM-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over