11-10455366-G-T

Variant names:

• chr11-10455366-G-T
• rs28403593
• NM_001025389.2:c.-88G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.28
• Publications: 5 publications found

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]

AMPD3 Gene-Disease associations (from GenCC):

• adenosine monophosphate deaminase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
AMPD3	NM_001025389.2	c.-88G>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000396553.7	NP_001020560.1
AMPD3	NM_000480.3	c.22+4323G>T		intron_variant	Intron 1 of 14		NP_000471.1
AMPD3	NM_001172431.2	c.-278+4851G>T		intron_variant	Intron 1 of 13		NP_001165902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000396553.7	c.-88G>T		5_prime_UTR_variant	Exon 1 of 15	1	NM_001025389.2	ENSP00000379801.2

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

African (AFR) AF: 0.0704 AC: 1112 AN: 15786

American (AMR) AF: 0.138 AC: 136 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 565 AN: 5152

East Asian (EAS) AF: 0.119 AC: 434 AN: 3632

South Asian (SAS) AF: 0.177 AC: 2914 AN: 16460

European-Finnish (FIN) AF: 0.239 AC: 67 AN: 280

Middle Eastern (MID) AF: 0.139 AC: 226 AN: 1622

European-Non Finnish (NFE) AF: 0.201 AC: 153450 AN: 761968

Other (OTH) AF: 0.189 AC: 5170 AN: 27304

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

African (AFR) AF: 0.0768 AC: 3190 AN: 41510

American (AMR) AF: 0.140 AC: 2140 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3472

East Asian (EAS) AF: 0.116 AC: 599 AN: 5162

South Asian (SAS) AF: 0.179 AC: 862 AN: 4824

European-Finnish (FIN) AF: 0.229 AC: 2420 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13319 AN: 67976

Other (OTH) AF: 0.149 AC: 316 AN: 2114

Alfa AF: 0.184 Hom.: 370

Bravo AF: 0.142

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Erythrocyte AMP deaminase deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		1.3
PromoterAI		0.065	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28403593; hg19: chr11-10476913;