11-10455151-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The ENST00000396554.7(AMPD3):c.22+4108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 985,268 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (505 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1789 hom.)
• Consequence: AMPD3 ENST00000396554.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 11-10455151-C-T is Benign according to our data. Variant chr11-10455151-C-T is described in ClinVar as [Benign]. Clinvar id is 302138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMPD3	NM_000480.3	c.22+4108C>T		intron_variant
AMPD3	NM_001172431.2	c.-278+4636C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMPD3	ENST00000396554.7	c.22+4108C>T		intron_variant		1		A1
AMPD3	ENST00000524866.5	c.-114-189C>T		intron_variant		1
AMPD3	ENST00000534047.5	c.22+4108C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10875 AN: 152094 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0780

GnomAD4 exome AF: 0.0589 AC: 49070 AN: 833056 Hom.: 1789 Cov.: 32 AF XY: 0.0595 AC XY: 22905 AN XY: 384692

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.0579

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.0774

GnomAD4 genome AF: 0.0716 AC: 10902 AN: 152212 Hom.: 505 Cov.: 32 AF XY: 0.0731 AC XY: 5444 AN XY: 74432

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0543

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0601 Hom.: 68

Bravo AF: 0.0712

Asia WGS AF: 0.194 AC: 672 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	-0.17
Cadd	Benign	17
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071019; hg19: chr11-10476698;