chr1-114692389-C-A

Variant names:

• chr1-114692389-C-A
• rs2010899
• NM_000036.3:c.34+1047G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000036.3(AMPD1):​c.34+1047G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,130 control chromosomes in the GnomAD database, including 32,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32260 hom., cov: 33)
• Consequence: AMPD1 NM_000036.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000036.3. 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
	AMPD1	NM_000036.3	MANE Select	c.34+1047G>T		intron	N/A	NP_000027.3	P23109-1
	AMPD1	NM_001172626.2		c.22+3061G>T		intron	N/A	NP_001166097.2	P23109-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD1	ENST00000520113.7	TSL:1 MANE Select	c.34+1047G>T		intron	N/A	ENSP00000430075.3	P23109-1
	AMPD1	ENST00000369538.4	TSL:2	c.22+3061G>T		intron	N/A	ENSP00000358551.4	P23109-2
	AMPD1	ENST00000637080.1	TSL:5	n.37+3048G>T		intron	N/A	ENSP00000489753.1	A0A1B0GTL6

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97077 AN: 152012 Hom.: 32207 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.628

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.639 AC: 97194 AN: 152130 Hom.: 32260 Cov.: 33 AF XY: 0.648 AC XY: 48211 AN XY: 74374

African (AFR) AF: 0.735 AC: 30488 AN: 41492

American (AMR) AF: 0.709 AC: 10837 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5186

South Asian (SAS) AF: 0.783 AC: 3783 AN: 4830

European-Finnish (FIN) AF: 0.641 AC: 6779 AN: 10572

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36364 AN: 67986

Other (OTH) AF: 0.633 AC: 1338 AN: 2114

Alfa AF: 0.561 Hom.: 37304

Bravo AF: 0.649

Asia WGS AF: 0.881 AC: 3062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.64
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs2010899; hg19: chr1-115235010;