rs147309598

Variant names:

• chr2-218270141-T-A
• rs147309598
• ENST00000444053.5:c.-55A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180
• Publications: 1 publications found

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]

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 Gene-Disease associations (from GenCC):

• paroxysmal nonkinesigenic dyskinesia 1

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• Tourette syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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 VariationId is 1201202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444053.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAMP	NM_001087.5	MANE Select	c.-55A>T		upstream_gene	N/A	NP_001078.2	Q13685
	AAMP	NM_001302545.2		c.-55A>T		upstream_gene	N/A	NP_001289474.1	C9JEH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAMP	ENST00000444053.5	TSL:1	c.-55A>T		5_prime_UTR	Exon 1 of 11	ENSP00000403343.1	C9JEH3
	AAMP	ENST00000912377.1		c.-55A>T		5_prime_UTR	Exon 1 of 11	ENSP00000582436.1
	AAMP	ENST00000952043.1		c.-55A>T		5_prime_UTR	Exon 1 of 11	ENSP00000622102.1

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152194 Hom.: 6 Cov.: 32

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.: 43 Cov.: 32 AF XY: 0.00716 AC XY: 5123 AN XY: 715892

African (AFR) AF: 0.00116 AC: 38 AN: 32736

American (AMR) AF: 0.00189 AC: 80 AN: 42430

Ashkenazi Jewish (ASJ) AF: 0.00368 AC: 92 AN: 25032

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39342

South Asian (SAS) AF: 0.00390 AC: 330 AN: 84538

European-Finnish (FIN) AF: 0.00447 AC: 233 AN: 52132

Middle Eastern (MID) AF: 0.000709 AC: 4 AN: 5638

European-Non Finnish (NFE) AF: 0.00842 AC: 9273 AN: 1100978

Other (OTH) AF: 0.00648 AC: 385 AN: 59430

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152312 Hom.: 6 Cov.: 32 AF XY: 0.00474 AC XY: 353 AN XY: 74482

African (AFR) AF: 0.000938 AC: 39 AN: 41580

American (AMR) AF: 0.000915 AC: 14 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4826

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00916 AC: 623 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00752 Hom.: 0

Bravo AF: 0.00473

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		-0.018
PromoterAI		-0.00030	Neutral
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

Other links and lift over

dbSNP: rs147309598; hg19: chr2-219134864;