Variant 1-114684369-CAAAA-CAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The NM_000036.3(AMPD1):c.382-6_382-5insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 961,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.046 ( 0 hom. )

Consequence

AMPD1
NM_000036.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

AMPD1 (HGNC:468): (adenosine monophosphate deaminase 1) Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

AMPD1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 1-114684369-C-CA is Benign according to our data. Variant chr1-114684369-C-CA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 291934.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0461 (38149/827386) while in subpopulation AFR AF= 0.0521 (986/18918). AF 95% confidence interval is 0.0494. There are 0 homozygotes in gnomad4_exome. There are 18359 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD1	NM_000036.3 linkuse as main transcript	c.382-6_382-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000520113.7
AMPD1	NM_001172626.2 linkuse as main transcript	c.370-6_370-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD1	ENST00000520113.7 linkuse as main transcript	c.382-6_382-5insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000036.3	P4	P23109-1

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

153

AN:

134380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000528

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000422

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00219

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000275

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0461

AC:

38149

AN:

827386

Hom.:

Cov.:

AF XY:

0.0444

AC XY:

18359

AN XY:

413154

show subpopulations

Gnomad4 AFR exome

AF:

0.0521

Gnomad4 AMR exome

AF:

0.0466

Gnomad4 ASJ exome

AF:

0.0442

Gnomad4 EAS exome

AF:

0.0461

Gnomad4 SAS exome

AF:

0.0361

Gnomad4 FIN exome

AF:

0.0467

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0486

GnomAD4 genome

AF:

0.00113

AC:

152

AN:

134414

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

64854

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.000527

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000424

Gnomad4 SAS

AF:

0.00143

Gnomad4 FIN

AF:

0.00219

Gnomad4 NFE

AF:

0.000275

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Muscle AMP deaminase deficiency

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2023	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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