11-10323889-A-G

Variant names:

• chr11-10323889-A-G
• rs16907654
• ENST00000527261.5:n.362-6681A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532250.5(AMPD3):​c.-146+6121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,312 control chromosomes in the GnomAD database, including 936 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (936 hom., cov: 32)
• Consequence: AMPD3 ENST00000532250.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 6 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

CAND1.11 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532250.5. 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
	CAND1.11	NR_103765.1		n.362-6681A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000527261.5	TSL:1	n.362-6681A>G		intron	N/A
	AMPD3	ENST00000902501.1		c.-145-6681A>G		intron	N/A	ENSP00000572560.1
	AMPD3	ENST00000930062.1		c.-262-6681A>G		intron	N/A	ENSP00000600121.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15362 AN: 152194 Hom.: 937 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0960

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15367 AN: 152312 Hom.: 936 Cov.: 32 AF XY: 0.105 AC XY: 7811 AN XY: 74460

African (AFR) AF: 0.0738 AC: 3067 AN: 41578

American (AMR) AF: 0.0805 AC: 1232 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0669 AC: 323 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2455 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7657 AN: 68032

Other (OTH) AF: 0.0950 AC: 201 AN: 2116

Alfa AF: 0.0626 Hom.: 89

Bravo AF: 0.0892

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.49
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs16907654; hg19: chr11-10345436;