Genetic Variant NM_000036.3:c.382-7_382-6dupTT (chr1-114684369-C-CAA) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000036.3(AMPD1):c.382-7_382-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AMPD1
NM_000036.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

myopathy due to myoadenylate deaminase deficiency
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
adenosine monophosphate deaminase deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AMPD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 1-114684369-C-CAA is Benign according to our data. Variant chr1-114684369-C-CAA is described in ClinVar as [Benign]. Clinvar id is 3697068.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD1	NM_000036.3 link	c.382-7_382-6dupTT		splice_region_variant, intron_variant	Intron 4 of 15	ENST00000520113.7	NP_000027.3	P23109-1
AMPD1	NM_001172626.2 link	c.370-7_370-6dupTT		splice_region_variant, intron_variant	Intron 3 of 14		NP_001166097.2	P23109-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD1	ENST00000520113.7 link	c.382-6_382-5insTT		splice_region_variant, intron_variant	Intron 4 of 15	1	NM_000036.3	ENSP00000430075.3		P23109-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

134468

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000368

AC:

AN:

70624

AF XY:

0.000376

show subpopulations

Gnomad AFR exome

AF:

0.000209

Gnomad AMR exome

AF:

0.000218

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.000732

Gnomad NFE exome

AF:

0.000267

Gnomad OTH exome

AF:

0.000579

GnomAD4 exome

AF:

0.0000258

AC:

AN:

1124844

Hom.:

Cov.:

AF XY:

0.0000213

AC XY:

AN XY:

563056

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000388

AC:

AN:

25780

American (AMR)

AF:

0.0000554

AC:

AN:

36114

Ashkenazi Jewish (ASJ)

AF:

0.0000481

AC:

AN:

20776

East Asian (EAS)

AF:

0.00

AC:

AN:

31084

South Asian (SAS)

AF:

0.000112

AC:

AN:

71710

European-Finnish (FIN)

AF:

0.0000977

AC:

AN:

40928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4764

European-Non Finnish (NFE)

AF:

0.0000130

AC:

AN:

846980

Other (OTH)

AF:

0.0000428

AC:

AN:

46708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.246

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

134468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64858

African (AFR)

AF:

0.00

AC:

AN:

36554

American (AMR)

AF:

0.00

AC:

AN:

13274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3220

East Asian (EAS)

AF:

0.00

AC:

AN:

4738

South Asian (SAS)

AF:

0.00

AC:

AN:

4210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61778

Other (OTH)

AF:

0.00

AC:

AN:

1808

Alfa

AF:

0.000556

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Muscle AMP deaminase deficiency

Benign:1

Oct 10, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over