rs2268699

Variant names:

• chr1-114685275-A-C
• rs2268699
• NM_000036.3:c.382-911T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-114685275-A-C
• chr1-114685275-A-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.382-911T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,968 control chromosomes in the GnomAD database, including 15,860 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 0.45 (15860 hom., cov: 31)
• Consequence: AMPD1 NM_000036.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD1	NM_000036.3	c.382-911T>G		intron_variant	Intron 4 of 15	ENST00000520113.7	NP_000027.3
AMPD1	NM_001172626.2	c.370-911T>G		intron_variant	Intron 3 of 14		NP_001166097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD1	ENST00000520113.7	c.382-911T>G		intron_variant	Intron 4 of 15	1	NM_000036.3	ENSP00000430075.3
AMPD1	ENST00000369538.4	c.370-911T>G		intron_variant	Intron 3 of 14	2		ENSP00000358551.4
AMPD1	ENST00000485564.3	n.256-911T>G		intron_variant	Intron 1 of 2	5
AMPD1	ENST00000637080.1	n.385-911T>G		intron_variant	Intron 3 of 13	5		ENSP00000489753.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67948 AN: 151850 Hom.: 15839 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.448 AC: 68021 AN: 151968 Hom.: 15860 Cov.: 31 AF XY: 0.452 AC XY: 33562 AN XY: 74290

African (AFR) AF: 0.542 AC: 22454 AN: 41430

American (AMR) AF: 0.463 AC: 7070 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2614 AN: 5156

South Asian (SAS) AF: 0.532 AC: 2565 AN: 4818

European-Finnish (FIN) AF: 0.475 AC: 5012 AN: 10556

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26104 AN: 67954

Other (OTH) AF: 0.387 AC: 818 AN: 2114

Alfa AF: 0.385 Hom.: 6195

Bravo AF: 0.448

Asia WGS AF: 0.548 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.066
DANN	Benign	0.69
PhyloP100		-1.1
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: rs2268699; hg19: chr1-115227896;