Variant 11-10456392-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001025389.2(AMPD3):c.-6+944G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,613,844 control chromosomes in the GnomAD database, including 3 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 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 2 hom. )

Consequence

AMPD3
NM_001025389.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044176877).

BP6

Variant 11-10456392-G-T is Benign according to our data. Variant chr11-10456392-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3035621.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AMPD3	NM_001025389.2 linkuse as main transcript	c.-6+944G>T		intron_variant		ENST00000396553.7
AMPD3	NM_001025390.2 linkuse as main transcript	c.6G>T	p.Glu2Asp	missense_variant	1/15
AMPD3	NM_000480.3 linkuse as main transcript	c.23-5123G>T		intron_variant
AMPD3	NM_001172431.2 linkuse as main transcript	c.-277-5123G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396553.7 linkuse as main transcript	c.-6+944G>T		intron_variant		1	NM_001025389.2	P4	Q01432-1

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

442

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

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:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000800

AC:

199

AN:

248686

Hom.:

AF XY:

0.000697

AC XY:

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000435

AC:

636

AN:

1461470

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

274

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00296

AC:

451

AN:

152374

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.00363

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00977

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000992

AC:

120

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AMPD3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 04, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

Cadd

Benign

2.7

Dann

Benign

0.97

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.34

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.12

MutPred

0.17

Loss of glycosylation at P3 (P = 0.1056);

MVP

0.30

ClinPred

0.0032

GERP RS

-4.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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