Variant rs587779378 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000036.3(AMPD1):c.-30G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AMPD1
NM_000036.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12877256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD1	NM_000036.3 linkuse as main transcript	c.-30G>A		5_prime_UTR_variant	1/16	ENST00000520113.7	NP_000027.3	P23109-1
AMPD1	NM_001172626.2 linkuse as main transcript	c.-30G>A		5_prime_UTR_variant	1/15		NP_001166097.2	P23109-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMPD1	ENST00000520113.7 linkuse as main transcript	c.-30G>A	5_prime_UTR_variant	1/16	1	NM_000036.3	ENSP00000430075.3	P23109-1
AMPD1	ENST00000369538.4 linkuse as main transcript	c.-30G>A	5_prime_UTR_variant	1/15	2		ENSP00000358551.4	P23109-2
AMPD1	ENST00000637080.1 linkuse as main transcript	n.-28G>A	upstream_gene_variant		5		ENSP00000489753.1	A0A1B0GTL6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autism

Uncertain:1

Uncertain significance, criteria provided, single submitter

reference population

State Key Lab of Medical Genetics, Central South University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.43

N;N

REVEL

Benign

0.14

Sift

Benign

0.10

T;D

Sift4G

Benign

0.48

T;T

Vest4

0.19

MutPred

0.29

Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);

MVP

0.83

MPC

0.081

ClinPred

0.12

GERP RS

2.3

Varity_R

0.052

gMVP

0.12

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