rs6484218

Variant names:

• chr11-10369034-G-A
• rs6484218
• ENST00000295663.9:n.51-23248G>A

Variant summary

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

The ENST00000532250.5(AMPD3):​c.-6+38325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,036 control chromosomes in the GnomAD database, including 4,260 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 0.21 (4260 hom., cov: 32)
• Consequence: AMPD3 ENST00000532250.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 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.501+38325G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000295663.9	TSL:1	n.51-23248G>A		intron	N/A
	AMPD3	ENST00000527261.5	TSL:1	n.501+38325G>A		intron	N/A
	AMPD3	ENST00000532966.1	TSL:1	n.119+11643G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31940 AN: 151918 Hom.: 4247 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.210 AC: 31993 AN: 152036 Hom.: 4260 Cov.: 32 AF XY: 0.213 AC XY: 15822 AN XY: 74316

African (AFR) AF: 0.369 AC: 15290 AN: 41424

American (AMR) AF: 0.148 AC: 2258 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5164

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1716 AN: 10582

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8920 AN: 67982

Other (OTH) AF: 0.200 AC: 422 AN: 2106

Alfa AF: 0.155 Hom.: 9050

Bravo AF: 0.218

Asia WGS AF: 0.280 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.70
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs6484218; hg19: chr11-10390581;