11-10455142-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000396554.7(AMPD3):c.22+4099A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 984,754 control chromosomes in the GnomAD database, including 175,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27711 hom., cov: 31)
  • Exomes 𝑓: 0.60 (148201 hom.)
• Consequence: AMPD3 ENST00000396554.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-10455142-A-G is Benign according to our data. Variant chr11-10455142-A-G is described in ClinVar as [Benign]. Clinvar id is 302137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD3	NM_000480.3	c.22+4099A>G		intron_variant
AMPD3	NM_001172431.2	c.-278+4627A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396554.7	c.22+4099A>G		intron_variant		1		A1
AMPD3	ENST00000524866.5	c.-114-198A>G		intron_variant		1
AMPD3	ENST00000534047.5	c.22+4099A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91252 AN: 151780 Hom.: 27699 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.596 AC: 496036 AN: 832856 Hom.: 148201 Cov.: 30 AF XY: 0.596 AC XY: 229207 AN XY: 384606

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.779

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.595

GnomAD4 genome AF: 0.601 AC: 91307 AN: 151898 Hom.: 27711 Cov.: 31 AF XY: 0.601 AC XY: 44613 AN XY: 74242

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.609

Alfa AF: 0.594 Hom.: 5934

Bravo AF: 0.612

Asia WGS AF: 0.573 AC: 1996 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	-0.29
Cadd	Benign	19
Dann	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs899013; hg19: chr11-10476689;