Genetic Variant AAMP:c.-55A>T (chr2-218270141-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000444053.5(AAMP):c.-55A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,594,568 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 43 hom. )

Consequence

AAMP
ENST00000444053.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0180

Variant links:

Genes affected

AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]

AAMP links:

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

PNKD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 2-218270141-T-A is Benign according to our data. Variant chr2-218270141-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1201202.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAMP	NM_001087.5 link	c.-55A>T		upstream_gene_variant		ENST00000248450.9	NP_001078.2	Q13685
AAMP	NM_001302545.2 link	c.-55A>T		upstream_gene_variant			NP_001289474.1	C9JEH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AAMP	ENST00000248450.9 link	c.-55A>T		upstream_gene_variant		1	NM_001087.5	ENSP00000248450.4		Q13685

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

776

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.00724

AC:

10436

AN:

1442256

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

5123

AN XY:

715892

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

AC:

AN:

32736

Gnomad4 AMR exome

AF:

0.00189

AC:

AN:

42430

Gnomad4 ASJ exome

AF:

0.00368

AC:

AN:

25032

Gnomad4 EAS exome

AF:

0.0000254

AC:

AN:

39342

Gnomad4 SAS exome

AF:

0.00390

AC:

330

AN:

84538

Gnomad4 FIN exome

AF:

0.00447

AC:

233

AN:

52132

Gnomad4 NFE exome

AF:

0.00842

AC:

9273

AN:

1100978

Gnomad4 Remaining exome

AF:

0.00648

AC:

385

AN:

59430

Heterozygous variant carriers

598

1196

1795

2393

2991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.00509

AC:

776

AN:

152312

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000938

AC:

0.000937951

AN:

0.000937951

Gnomad4 AMR

AF:

0.000915

AC:

0.000914554

AN:

0.000914554

Gnomad4 ASJ

AF:

0.00576

AC:

0.00576037

AN:

0.00576037

Gnomad4 EAS

AF:

0.000193

AC:

0.000193424

AN:

0.000193424

Gnomad4 SAS

AF:

0.00414

AC:

0.00414422

AN:

0.00414422

Gnomad4 FIN

AF:

0.00339

AC:

0.00339175

AN:

0.00339175

Gnomad4 NFE

AF:

0.00916

AC:

0.0091588

AN:

0.0091588

Gnomad4 OTH

AF:

0.00284

AC:

0.00283554

AN:

0.00283554

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00752

Hom.:

Bravo

AF:

0.00473

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 02, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism

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