Variant 1-114688677-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.271

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.99A>G	p.Gly33=	synonymous_variant	3/16	ENST00000520113.7	NP_000027.3
AMPD1	NM_001172626.2 linkuse as main transcript	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 linkuse as main transcript	c.99A>G	p.Gly33=	synonymous_variant	3/16	1	NM_000036.3	ENSP00000430075	P4	P23109-1
AMPD1	ENST00000369538.4 linkuse as main transcript	c.87A>G	p.Gly29=	synonymous_variant	2/15	2		ENSP00000358551	A1	P23109-2
AMPD1	ENST00000637080.1 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00267

AC XY:

363

AN XY:

135906

show subpopulations

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.:

Cov.:

AF XY:

0.00451

AC XY:

3282

AN XY:

727240

show subpopulations

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.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74490

show subpopulations

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.:

Bravo

AF:

0.00267

Asia WGS

AF:

0.000866

AC:

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over