chr11-10455403-AGCCAGC-A

Position:

• chr11-10455403-AGCCAGC-A

Variant summary

Our verdict is Likely benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMPD3	NM_001025389.2	c.-48_-43delCAGCGC		5_prime_UTR_variant	1/15	ENST00000396553.7	NP_001020560.1
AMPD3	NM_000480.3	c.22+4363_22+4368delCAGCGC		intron_variant			NP_000471.1
AMPD3	NM_001172431.2	c.-278+4891_-278+4896delCAGCGC		intron_variant			NP_001165902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000396553	c.-48_-43delCAGCGC		5_prime_UTR_variant	1/15	1	NM_001025389.2	ENSP00000379801.2

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

Gnomad4 AFR exome AF: 0.000317

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00357

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.000842

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

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.000725

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Erythrocyte AMP deaminase deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs547362583; hg19: chr11-10476950;