11-10455351-T-C

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.-103T>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 0.713 in 985,192 control chromosomes in the GnomAD database, including 251,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40178 hom., cov: 30)
  • Exomes 𝑓: 0.71 (211115 hom.)
• Consequence: AMPD3 NM_001025389.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.715

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 11-10455351-T-C is Benign according to our data. Variant chr11-10455351-T-C is described in ClinVar as [Benign]. Clinvar id is 302142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD3	NM_001025389.2	c.-103T>C		5_prime_UTR_variant	1/15	ENST00000396553.7
AMPD3	NM_000480.3	c.22+4308T>C		intron_variant
AMPD3	NM_001172431.2	c.-278+4836T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396553.7	c.-103T>C		5_prime_UTR_variant	1/15	1	NM_001025389.2	P4

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110298 AN: 151908 Hom.: 40159 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.711 AC: 592526 AN: 833166 Hom.: 211115 Cov.: 49 AF XY: 0.711 AC XY: 273536 AN XY: 384754

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.784

Gnomad4 ASJ exome AF: 0.749

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.709

Gnomad4 NFE exome AF: 0.713

Gnomad4 OTH exome AF: 0.703

GnomAD4 genome AF: 0.726 AC: 110364 AN: 152026 Hom.: 40178 Cov.: 30 AF XY: 0.724 AC XY: 53818 AN XY: 74314

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.719

Alfa AF: 0.724 Hom.: 52975

Bravo AF: 0.735

Asia WGS AF: 0.638 AC: 2222 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	9.4
Dann	Benign	0.81

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: rs899011; hg19: chr11-10476898;