1-114695540-G-A

Variant names:

• chr1-114695540-G-A
• rs587779375
• NM_000036.3:c.-69C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000036.3(AMPD1):​c.-69C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD1 NM_000036.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD1	NM_000036.3	MANE Select	c.-69C>T		5_prime_UTR	Exon 1 of 16	NP_000027.3
	AMPD1	NM_001172626.2		c.-69C>T		5_prime_UTR	Exon 1 of 15	NP_001166097.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD1	ENST00000520113.7	TSL:1 MANE Select	c.-69C>T		5_prime_UTR	Exon 1 of 16	ENSP00000430075.3
	AMPD1	ENST00000369538.4	TSL:2	c.-69C>T		5_prime_UTR	Exon 1 of 15	ENSP00000358551.4
	AMPD1	ENST00000637080.1	TSL:5	n.-67C>T		upstream_gene	N/A	ENSP00000489753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.097	N
PhyloP100		1.4
Vest4		0.63
GERP RS		3.5
PromoterAI		0.0010	Neutral
Mutation Taster		=86/114	disease causing (fs/PTC)

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: rs587779375; hg19: chr1-115238161;