11-10455372-T-G

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.-82T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 985,162 control chromosomes in the GnomAD database, including 7,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1431 hom., cov: 31)
  • Exomes 𝑓: 0.12 (5621 hom.)
• Consequence: AMPD3 NM_001025389.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.542

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 11-10455372-T-G is Benign according to our data. Variant chr11-10455372-T-G is described in ClinVar as [Benign]. Clinvar id is 302144.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD3	NM_001025389.2	c.-82T>G		5_prime_UTR_variant	1/15	ENST00000396553.7
AMPD3	NM_000480.3	c.22+4329T>G		intron_variant
AMPD3	NM_001172431.2	c.-278+4857T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396553.7	c.-82T>G		5_prime_UTR_variant	1/15	1	NM_001025389.2	P4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19765 AN: 151880 Hom.: 1431 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.116 AC: 96692 AN: 833164 Hom.: 5621 Cov.: 40 AF XY: 0.115 AC XY: 44410 AN XY: 384768

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.0917

Gnomad4 EAS exome AF: 0.000551

Gnomad4 SAS exome AF: 0.0859

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.130 AC: 19778 AN: 151998 Hom.: 1431 Cov.: 31 AF XY: 0.128 AC XY: 9518 AN XY: 74290

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0999

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.117

Alfa AF: 0.124 Hom.: 209

Bravo AF: 0.129

Asia WGS AF: 0.0670 AC: 232 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 12, 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	7.7
Dann	Benign	0.80

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: rs58115104; hg19: chr11-10476919;