rs4444073

Variant names:

• chr11-10310117-A-C
• rs4444073
• ENST00000527261.5:n.361+1444A>C

Variant summary

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

The ENST00000902501.1(AMPD3):​c.-146+1444A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,950 control chromosomes in the GnomAD database, including 12,086 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 0.38 (12086 hom., cov: 32)
• Consequence: AMPD3 ENST00000902501.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 9 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000902501.1. 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.361+1444A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000527261.5	TSL:1	n.361+1444A>C		intron	N/A
	AMPD3	ENST00000902501.1		c.-146+1444A>C		intron	N/A	ENSP00000572560.1
	AMPD3	ENST00000930062.1		c.-263+1444A>C		intron	N/A	ENSP00000600121.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57605 AN: 151828 Hom.: 12082 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.379 AC: 57632 AN: 151950 Hom.: 12086 Cov.: 32 AF XY: 0.381 AC XY: 28295 AN XY: 74248

African (AFR) AF: 0.217 AC: 8977 AN: 41454

American (AMR) AF: 0.418 AC: 6392 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1232 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5168

South Asian (SAS) AF: 0.315 AC: 1518 AN: 4820

European-Finnish (FIN) AF: 0.501 AC: 5275 AN: 10524

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31757 AN: 67920

Other (OTH) AF: 0.356 AC: 753 AN: 2114

Alfa AF: 0.414 Hom.: 2293

Bravo AF: 0.363

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.57

Splicing

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

Other links and lift over

dbSNP: rs4444073; hg19: chr11-10331664;