11-10367235-A-G

Variant names:

• chr11-10367235-A-G
• rs2923084
• ENST00000295663.9:n.51-25047A>G

Variant summary

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

The ENST00000295663.9(AMPD3):​n.51-25047A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,134 control chromosomes in the GnomAD database, including 8,091 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 0.29 (8091 hom., cov: 32)
• Consequence: AMPD3 ENST00000295663.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 72 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.501+36526A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000295663.9	n.51-25047A>G		intron_variant	Intron 1 of 2	1
AMPD3	ENST00000527261.5	n.501+36526A>G		intron_variant	Intron 2 of 2	1
AMPD3	ENST00000532966.1	n.119+9844A>G		intron_variant	Intron 1 of 1	1
AMPD3	ENST00000532250.5	c.-6+36526A>G		intron_variant	Intron 2 of 3	4		ENSP00000432707.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44158 AN: 152016 Hom.: 8079 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.291 AC: 44207 AN: 152134 Hom.: 8091 Cov.: 32 AF XY: 0.290 AC XY: 21590 AN XY: 74376

African (AFR) AF: 0.471 AC: 19554 AN: 41474

American (AMR) AF: 0.408 AC: 6244 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3472

East Asian (EAS) AF: 0.506 AC: 2616 AN: 5170

South Asian (SAS) AF: 0.128 AC: 619 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1444 AN: 10608

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12169 AN: 67980

Other (OTH) AF: 0.285 AC: 602 AN: 2112

Alfa AF: 0.221 Hom.: 21237

Bravo AF: 0.323

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.40
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2923084; hg19: chr11-10388782;