1-114684369-CAAAA-CAAAAAAAAA

Variant names:

• chr1-114684369-C-CAAAAA
• rs727503806
• NM_000036.3:c.382-10_382-6dupTTTTT

Variant summary

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

The NM_000036.3(AMPD1):​c.382-10_382-6dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMPD1 NM_000036.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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 0 ACMG points.

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.382-10_382-6dupTTTTT		splice_region intron	N/A	NP_000027.3	P23109-1
	AMPD1	NM_001172626.2		c.370-10_370-6dupTTTTT		splice_region 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.382-6_382-5insTTTTT		splice_region intron	N/A	ENSP00000430075.3	P23109-1
	AMPD1	ENST00000369538.4	TSL:2	c.370-6_370-5insTTTTT		splice_region intron	N/A	ENSP00000358551.4	P23109-2
	AMPD1	ENST00000485564.3	TSL:5	n.256-6_256-5insTTTTT		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 134466 Hom.: 0 Cov.: 32

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

GnomAD4 exome AF: 0.00000887 AC: 10 AN: 1126824 Hom.: 0 Cov.: 0 AF XY: 0.00000887 AC XY: 5 AN XY: 564006

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

African (AFR) AF: 0.0000387 AC: 1 AN: 25830

American (AMR) AF: 0.000138 AC: 5 AN: 36182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20808

East Asian (EAS) AF: 0.00 AC: 0 AN: 31134

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4768

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 848542

Other (OTH) AF: 0.0000428 AC: 2 AN: 46780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 134466 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 64856

African (AFR) AF: 0.00 AC: 0 AN: 36554

American (AMR) AF: 0.00 AC: 0 AN: 13274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3220

East Asian (EAS) AF: 0.00 AC: 0 AN: 4738

South Asian (SAS) AF: 0.00 AC: 0 AN: 4210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61778

Other (OTH) AF: 0.00 AC: 0 AN: 1808

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs727503806;

hg19: chr1-115226990;