rs547362583

Variant names:

• chr11-10455403-AGCCAGC-A
• rs547362583
• NM_001025389.2:c.-48_-43delCAGCGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001025389.2(AMPD3):​c.-48_-43delCAGCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 985,268 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: AMPD3 NM_001025389.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025389.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	NM_001025389.2	MANE Select	c.-48_-43delCAGCGC		5_prime_UTR	Exon 1 of 15	NP_001020560.1	Q01432-1
	AMPD3	NM_000480.3		c.22+4363_22+4368delCAGCGC		intron	N/A	NP_000471.1	Q01432-4
	AMPD3	NM_001172431.2		c.-278+4891_-278+4896delCAGCGC		intron	N/A	NP_001165902.1	Q01432-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000396553.7	TSL:1 MANE Select	c.-48_-43delCAGCGC		5_prime_UTR	Exon 1 of 15	ENSP00000379801.2	Q01432-1
	AMPD3	ENST00000524866.5	TSL:1	c.-48_-43delCAGCGC		5_prime_UTR	Exon 2 of 6	ENSP00000433284.1	E9PLK6
	AMPD3	ENST00000396554.7	TSL:1	c.22+4363_22+4368delCAGCGC		intron	N/A	ENSP00000379802.3	Q01432-4

Frequencies

GnomAD3 genomes AF: 0.000599 AC: 91 AN: 151940 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00135 AC: 1125 AN: 833210 Hom.: 2 AF XY: 0.00139 AC XY: 536 AN XY: 384800

African (AFR) AF: 0.000317 AC: 5 AN: 15788

American (AMR) AF: 0.00203 AC: 2 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3632

South Asian (SAS) AF: 0.00 AC: 0 AN: 16460

European-Finnish (FIN) AF: 0.00357 AC: 1 AN: 280

Middle Eastern (MID) AF: 0.00123 AC: 2 AN: 1622

European-Non Finnish (NFE) AF: 0.00143 AC: 1092 AN: 761986

Other (OTH) AF: 0.000842 AC: 23 AN: 27306

GnomAD4 genome AF: 0.000598 AC: 91 AN: 152058 Hom.: 0 Cov.: 31 AF XY: 0.000565 AC XY: 42 AN XY: 74352

African (AFR) AF: 0.000217 AC: 9 AN: 41510

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 67956

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.000725

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Erythrocyte AMP deaminase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs547362583; hg19: chr11-10476950;