11-10455366-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001025389.2(AMPD3):c.-88G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 985,312 control chromosomes in the GnomAD database, including 18,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2093 hom., cov: 31)
  • Exomes 𝑓: 0.20 (16564 hom.)
• Consequence: AMPD3 NM_001025389.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-10455366-G-T is Benign according to our data. Variant chr11-10455366-G-T is described in ClinVar as [Benign]. Clinvar id is 302143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD3	NM_001025389.2	c.-88G>T		5_prime_UTR_variant	1/15	ENST00000396553.7
AMPD3	NM_000480.3	c.22+4323G>T		intron_variant
AMPD3	NM_001172431.2	c.-278+4851G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396553.7	c.-88G>T		5_prime_UTR_variant	1/15	1	NM_001025389.2	P4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23335 AN: 152006 Hom.: 2091 Cov.: 31

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.197 AC: 164074 AN: 833190 Hom.: 16564 Cov.: 43 AF XY: 0.197 AC XY: 75723 AN XY: 384774

Gnomad4 AFR exome AF: 0.0704

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.153 AC: 23339 AN: 152122 Hom.: 2093 Cov.: 31 AF XY: 0.154 AC XY: 11456 AN XY: 74354

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.149

Alfa AF: 0.188 Hom.: 367

Bravo AF: 0.142

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Erythrocyte AMP deaminase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	12
Dann	Benign	0.82

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

Other links and lift over

dbSNP: rs28403593; hg19: chr11-10476913;