Genetic Variant AMPD3:c.-157T>C (chr11-10455297-T-C) – 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.-157T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 985,376 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 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

AMPD3
NM_001025389.2 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.341

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:

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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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AMPD3	NM_001025389.2 link	c.-157T>C	5_prime_UTR_variant	Exon 1 of 15	ENST00000396553.7	NP_001020560.1	Q01432-1
AMPD3	NM_000480.3 link	c.22+4254T>C	intron_variant	Intron 1 of 14		NP_000471.1	Q01432-4
AMPD3	NM_001172431.2 link	c.-278+4782T>C	intron_variant	Intron 1 of 13		NP_001165902.1	Q01432-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000396553.7 link	c.-157T>C		5_prime_UTR_variant	Exon 1 of 15	1	NM_001025389.2	ENSP00000379801.2		Q01432-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.0000504

AC:

AN:

833162

Hom.:

Cov.:

AF XY:

0.0000364

AC XY:

AN XY:

384750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15788

American (AMR)

AF:

0.00

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

5154

East Asian (EAS)

AF:

0.00

AC:

AN:

3630

South Asian (SAS)

AF:

0.00

AC:

AN:

16460

European-Finnish (FIN)

AF:

0.00355

AC:

AN:

282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.0000433

AC:

AN:

761942

Other (OTH)

AF:

0.0000733

AC:

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000243

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68046

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000196

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.75

PhyloP100

-0.34

PromoterAI

0.00010

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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11-10455297-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over