rs2010899

chr1-114692389-C-Achr1-114692389-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD1	NM_000036.3	c.34+1047G>T		intron_variant		ENST00000520113.7
AMPD1	NM_001172626.2	c.22+3061G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD1	ENST00000520113.7	c.34+1047G>T		intron_variant		1	NM_000036.3	P4
AMPD1	ENST00000369538.4	c.22+3061G>T		intron_variant		2		A1
AMPD1	ENST00000637080.1	c.37+3048G>T		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.633

Alfa AF: 0.550 Hom.: 24044

Bravo AF: 0.649

Asia WGS AF: 0.881 AC: 3062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.88
Dann	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2010899; hg19: chr1-115235010;