rs61752480

Positions:

• chr1-114688677-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000036.3(AMPD1):​c.99A>G​(p.Gly33=) 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

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 -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 [Likely_benign]. Clinvar id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD1	NM_000036.3	c.99A>G	p.Gly33=	synonymous_variant	3/16	ENST00000520113.7	NP_000027.3
AMPD1	NM_001172626.2	c.87A>G	p.Gly29=	synonymous_variant	2/15		NP_001166097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD1	ENST00000520113.7	c.99A>G	p.Gly33=	synonymous_variant	3/16	1	NM_000036.3	ENSP00000430075	P4
AMPD1	ENST00000369538.4	c.87A>G	p.Gly29=	synonymous_variant	2/15	2		ENSP00000358551	A1
AMPD1	ENST00000637080.1	c.102A>G	p.Gly34=	synonymous_variant, NMD_transcript_variant	2/14	5		ENSP00000489753

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

GnomAD3 exomes AF: 0.00269 AC: 676 AN: 251472 Hom.: 3 AF XY: 0.00267 AC XY: 363 AN XY: 135906

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 SAS exome AF: 0.00124

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

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.00391

Gnomad4 NFE exome AF: 0.00549

Gnomad4 OTH exome AF: 0.00493

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

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00456

Gnomad4 OTH AF: 0.00142

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

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 29, 2015

- -

Muscle AMP deaminase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

AMPD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.7
DANN	Benign	0.57

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: rs61752480; hg19: chr1-115231298;