ENST00000295663.9:n.51-21949C>T

Variant names:

• chr11-10370333-C-T
• rs10770107
• ENST00000295663.9:n.51-21949C>T

Variant summary

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

The ENST00000295663.9(AMPD3):​n.51-21949C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,022 control chromosomes in the GnomAD database, including 44,244 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 0.74 (44244 hom., cov: 31)
• Consequence: AMPD3 ENST00000295663.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.501+39624C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000295663.9	n.51-21949C>T		intron_variant	Intron 1 of 2	1
AMPD3	ENST00000527261.5	n.501+39624C>T		intron_variant	Intron 2 of 2	1
AMPD3	ENST00000532966.1	n.119+12942C>T		intron_variant	Intron 1 of 1	1
AMPD3	ENST00000532250.5	c.-6+39624C>T		intron_variant	Intron 2 of 3	4		ENSP00000432707.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113008 AN: 151902 Hom.: 44238 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.744 AC: 113041 AN: 152022 Hom.: 44244 Cov.: 31 AF XY: 0.743 AC XY: 55192 AN XY: 74332

African (AFR) AF: 0.476 AC: 19707 AN: 41408

American (AMR) AF: 0.830 AC: 12677 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2975 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3580 AN: 5160

South Asian (SAS) AF: 0.764 AC: 3682 AN: 4822

European-Finnish (FIN) AF: 0.838 AC: 8861 AN: 10580

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 58989 AN: 67990

Other (OTH) AF: 0.764 AC: 1610 AN: 2108

Alfa AF: 0.822 Hom.: 159947

Bravo AF: 0.729

Asia WGS AF: 0.701 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		0.020

Splicing

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

Other links and lift over

dbSNP: rs10770107; hg19: chr11-10391880;