11-10455372-T-G

Variant names:

• chr11-10455372-T-G
• rs58115104
• NM_001025389.2:c.-82T>G

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.-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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.542
• 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 11-10455372-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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
AMPD3	NM_001025389.2	c.-82T>G		5_prime_UTR_variant	Exon 1 of 15	ENST00000396553.7	NP_001020560.1
AMPD3	NM_000480.3	c.22+4329T>G		intron_variant	Intron 1 of 14		NP_000471.1
AMPD3	NM_001172431.2	c.-278+4857T>G		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.-82T>G		5_prime_UTR_variant	Exon 1 of 15	1	NM_001025389.2	ENSP00000379801.2

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

African (AFR) AF: 0.190 AC: 3002 AN: 15788

American (AMR) AF: 0.0598 AC: 59 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 472 AN: 5150

East Asian (EAS) AF: 0.000551 AC: 2 AN: 3632

South Asian (SAS) AF: 0.0859 AC: 1414 AN: 16460

European-Finnish (FIN) AF: 0.144 AC: 40 AN: 278

Middle Eastern (MID) AF: 0.0875 AC: 142 AN: 1622

European-Non Finnish (NFE) AF: 0.116 AC: 88587 AN: 761948

Other (OTH) AF: 0.109 AC: 2974 AN: 27300

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

African (AFR) AF: 0.183 AC: 7575 AN: 41444

American (AMR) AF: 0.0999 AC: 1528 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3468

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5162

South Asian (SAS) AF: 0.0782 AC: 376 AN: 4810

European-Finnish (FIN) AF: 0.155 AC: 1636 AN: 10528

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7986 AN: 67974

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.125 Hom.: 227

Bravo AF: 0.129

Asia WGS AF: 0.0670 AC: 232 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 12, 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	7.7
DANN	Benign	0.80
PhyloP100		-0.54
PromoterAI		-0.29	Neutral
Mutation Taster		=294/6	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: rs58115104; hg19: chr11-10476919;