rs61752480

Variant names:

• chr1-114688677-T-C
• rs61752480
• NM_000036.3:c.99A>G
• AMPD1 p.Gly33Gly

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000036.3(AMPD1):​c.99A>G​(p.Gly33Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,614,210 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (34 hom.)
• Consequence: AMPD1 NM_000036.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.271
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-114688677-T-C is Benign according to our data. Variant chr1-114688677-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 92333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 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.99A>G	p.Gly33Gly	synonymous	Exon 3 of 16	NP_000027.3	P23109-1
	AMPD1	NM_001172626.2		c.87A>G	p.Gly29Gly	synonymous	Exon 2 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.99A>G	p.Gly33Gly	synonymous	Exon 3 of 16	ENSP00000430075.3	P23109-1
	AMPD1	ENST00000369538.4	TSL:2	c.87A>G	p.Gly29Gly	synonymous	Exon 2 of 15	ENSP00000358551.4	P23109-2
	AMPD1	ENST00000637080.1	TSL:5	n.102A>G		non_coding_transcript_exon	Exon 2 of 14	ENSP00000489753.1	A0A1B0GTL6

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152214 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00269 AC: 676 AN: 251472 AF XY: 0.00267

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00379

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00467 AC: 6831 AN: 1461878 Hom.: 34 Cov.: 32 AF XY: 0.00451 AC XY: 3282 AN XY: 727240

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00174 AC: 78 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00111 AC: 96 AN: 86252

European-Finnish (FIN) AF: 0.00391 AC: 209 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00549 AC: 6107 AN: 1112002

Other (OTH) AF: 0.00493 AC: 298 AN: 60396

GnomAD4 genome AF: 0.00305 AC: 464 AN: 152332 Hom.: 3 Cov.: 32 AF XY: 0.00305 AC XY: 227 AN XY: 74490

African (AFR) AF: 0.000818 AC: 34 AN: 41580

American (AMR) AF: 0.00471 AC: 72 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00456 AC: 310 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00393 Hom.: 0

Bravo AF: 0.00267

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Muscle AMP deaminase deficiency (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.7
DANN	Benign	0.57
PhyloP100		-0.27
Mutation Taster		=89/11	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

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

Other links and lift over

dbSNP: rs61752480;

hg19: chr1-115231298;