1-114688677-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000036.3(AMPD1):c.99A>G(p.Gly33Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,614,210 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 34 hom. )

Consequence

AMPD1
NM_000036.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.271

Publications

3 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-114688677-T-C is Benign according to our data. Variant chr1-114688677-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 92333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-114688677-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 92333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-114688677-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 92333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-114688677-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 92333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.271 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD1	NM_000036.3 link	c.99A>G	p.Gly33Gly	synonymous_variant	Exon 3 of 16	ENST00000520113.7	NP_000027.3	P23109-1
AMPD1	NM_001172626.2 link	c.87A>G	p.Gly29Gly	synonymous_variant	Exon 2 of 15		NP_001166097.2	P23109-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMPD1	ENST00000520113.7 link	c.99A>G	p.Gly33Gly	synonymous_variant	Exon 3 of 16	1	NM_000036.3	ENSP00000430075.3	P23109-1
AMPD1	ENST00000369538.4 link	c.87A>G	p.Gly29Gly	synonymous_variant	Exon 2 of 15	2		ENSP00000358551.4	P23109-2
AMPD1	ENST00000637080.1 link	n.102A>G		non_coding_transcript_exon_variant	Exon 2 of 14	5		ENSP00000489753.1	A0A1B0GTL6

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00456

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00269

AC:

676

AN:

251472

AF XY:

0.00267

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00379

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00467

AC:

6831

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

3282

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33480

American (AMR)

AF:

0.00174

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00111

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00391

AC:

209

AN:

53420

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00549

AC:

6107

AN:

1112002

Other (OTH)

AF:

0.00493

AC:

298

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

393

786

1180

1573

1966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.00305

AC:

464

AN:

152332

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41580

American (AMR)

AF:

0.00471

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00456

AC:

310

AN:

68034

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00393

Hom.:

Bravo

AF:

0.00267

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00491

EpiControl

AF:

0.00344

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 29, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Muscle AMP deaminase deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AMPD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.7

(source)

DANN

Benign

0.57

PhyloP100

-0.27

Mutation Taster

=89/11

polymorphism

(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

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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