rs7129220

Variant names:

• chr11-10328991-G-A
• rs7129220
• ENST00000527261.5:n.362-1579G>A

Variant summary

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

The ENST00000527261.5(AMPD3):​n.362-1579G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,164 control chromosomes in the GnomAD database, including 934 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 (934 hom., cov: 32)
• Consequence: AMPD3 ENST00000527261.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.362-1579G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000527261.5	n.362-1579G>A		intron_variant	Intron 1 of 2	1
AMPD3	ENST00000532250.5	c.-145-1579G>A		intron_variant	Intron 1 of 3	4		ENSP00000432707.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15259 AN: 152046 Hom.: 935 Cov.: 32

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0805

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.100 AC: 15266 AN: 152164 Hom.: 934 Cov.: 32 AF XY: 0.104 AC XY: 7732 AN XY: 74376

African (AFR) AF: 0.0739 AC: 3068 AN: 41524

American (AMR) AF: 0.0804 AC: 1229 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0494 AC: 238 AN: 4816

European-Finnish (FIN) AF: 0.232 AC: 2451 AN: 10572

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

European-Non Finnish (NFE) AF: 0.112 AC: 7648 AN: 68002

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.103 Hom.: 1928

Bravo AF: 0.0890

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.64
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs7129220; hg19: chr11-10350538;