NM_000036.3:c.552T>C

Variant names:

• chr1-114680474-A-G
• rs35197706
• NM_000036.3:c.552T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_000036.3(AMPD1):​c.552T>C​(p.Phe184Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,614,016 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (16 hom.)
• Consequence: AMPD1 NM_000036.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.16
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-114680474-A-G is Benign according to our data. Variant chr1-114680474-A-G is described in ClinVar as Benign. ClinVar VariationId is 529205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00604 (919/152274) while in subpopulation AFR AF = 0.0207 (862/41546). AF 95% confidence interval is 0.0196. There are 13 homozygotes in GnomAd4. There are 444 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.552T>C	p.Phe184Phe	synonymous	Exon 6 of 16	NP_000027.3	P23109-1
	AMPD1	NM_001172626.2		c.540T>C	p.Phe180Phe	synonymous	Exon 5 of 15	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.552T>C	p.Phe184Phe	synonymous	Exon 6 of 16	ENSP00000430075.3	P23109-1
	AMPD1	ENST00000369538.4	TSL:2	c.540T>C	p.Phe180Phe	synonymous	Exon 5 of 15	ENSP00000358551.4	P23109-2
	AMPD1	ENST00000639077.1	TSL:5	n.217T>C		non_coding_transcript_exon	Exon 3 of 13

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 919 AN: 152156 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

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: 0.0000735

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00151 AC: 379 AN: 251426 AF XY: 0.00115

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000625 AC: 914 AN: 1461742 Hom.: 16 Cov.: 31 AF XY: 0.000545 AC XY: 396 AN XY: 727208

African (AFR) AF: 0.0233 AC: 780 AN: 33470

American (AMR) AF: 0.000894 AC: 40 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111894

Other (OTH) AF: 0.00134 AC: 81 AN: 60394

GnomAD4 genome AF: 0.00604 AC: 919 AN: 152274 Hom.: 13 Cov.: 33 AF XY: 0.00596 AC XY: 444 AN XY: 74464

African (AFR) AF: 0.0207 AC: 862 AN: 41546

American (AMR) AF: 0.00275 AC: 42 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00481 Hom.: 9

Bravo AF: 0.00705

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Muscle AMP deaminase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism

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: rs35197706; hg19: chr1-115223095;