11-10487356-G-T

Position:

chr11-10487356-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000396553.7(AMPD3):c.931G>T(p.Val311Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0082 in 1,614,054 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V311M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0068 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 63 hom. )

Consequence

AMPD3
ENST00000396553.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 5.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015119016).

BP6

Variant 11-10487356-G-T is Benign according to our data. Variant chr11-10487356-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 166685.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}. Variant chr11-10487356-G-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD3	NM_001025389.2 linkuse as main transcript	c.931G>T	p.Val311Leu	missense_variant	6/15	ENST00000396553.7	NP_001020560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000396553.7 linkuse as main transcript	c.931G>T	p.Val311Leu	missense_variant	6/15	1	NM_001025389.2	ENSP00000379801	P4	Q01432-1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1036

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00672

AC:

1689

AN:

251464

Hom.:

AF XY:

0.00661

AC XY:

898

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.00924

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00835

AC:

12200

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

5948

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00290

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00964

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00680

AC:

1036

AN:

152290

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

489

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00840

Hom.:

Bravo

AF:

0.00557

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00733

AC:

890

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00782

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Erythrocyte AMP deaminase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 27, 2014

- -

AMPD3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2020

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Pathogenic

0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

.;.;D;.;D

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;.;D;D

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.5

.;.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Pathogenic

0.77

Sift

Uncertain

0.014

D;D;D;D;D

Sift4G

Uncertain

0.017

D;T;T;T;T

Polyphen

0.95

.;.;P;.;P

Vest4

0.78

MutPred

0.84

.;.;Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);

MVP

0.94

MPC

0.96

ClinPred

0.015

GERP RS

5.2

Varity_R

0.28

gMVP

0.67

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