Genetic Variant AMPD3:c.-25C>T (chr11-10455429-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025389.2(AMPD3):c.-25C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 972,178 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

AMPD3
NM_001025389.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.21

Publications

0 publications found

Variant links:

Genes affected

AMPD3 (HGNC:470): (adenosine monophosphate deaminase 3) This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]

AMPD3 Gene-Disease associations (from GenCC):

adenosine monophosphate deaminase deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AMPD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025389.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMPD3	NM_001025389.2	MANE Select	c.-25C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001020560.1	Q01432-1
AMPD3	NM_001025389.2	MANE Select	c.-25C>T	5_prime_UTR	Exon 1 of 15	NP_001020560.1	Q01432-1
AMPD3	NM_000480.3		c.22+4386C>T	intron	N/A	NP_000471.1	Q01432-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMPD3	ENST00000396553.7	TSL:1 MANE Select	c.-25C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000379801.2	Q01432-1
AMPD3	ENST00000524866.5	TSL:1	c.-25C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000433284.1	E9PLK6
AMPD3	ENST00000396553.7	TSL:1 MANE Select	c.-25C>T	5_prime_UTR	Exon 1 of 15	ENSP00000379801.2	Q01432-1

Frequencies

GnomAD3 genomes

AF:

0.00142

AC:

209

AN:

146880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000470

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:

0.000488

GnomAD4 exome

AF:

0.000101

AC:

AN:

825138

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

381222

show subpopulations

African (AFR)

AF:

0.00364

AC:

AN:

15652

American (AMR)

AF:

0.00

AC:

AN:

970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5098

East Asian (EAS)

AF:

0.00

AC:

AN:

3604

South Asian (SAS)

AF:

0.0000615

AC:

AN:

16268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

280

Middle Eastern (MID)

AF:

0.000623

AC:

AN:

1604

European-Non Finnish (NFE)

AF:

0.0000239

AC:

AN:

754618

Other (OTH)

AF:

0.000222

AC:

AN:

27044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00142

AC:

209

AN:

147040

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

71764

show subpopulations

African (AFR)

AF:

0.00496

AC:

201

AN:

40528

American (AMR)

AF:

0.000470

AC:

AN:

14906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4638

South Asian (SAS)

AF:

0.00

AC:

AN:

4290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66562

Other (OTH)

AF:

0.000483

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000925

Hom.:

Bravo

AF:

0.00151

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Erythrocyte AMP deaminase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-1.2

PromoterAI

-0.026

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over