NM_001025389.2:c.212C>A

Variant names:

• chr11-10461731-C-A
• NM_001025389.2:c.212C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025389.2(AMPD3):​c.212C>A​(p.Thr71Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPD3 NM_001025389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1883668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMPD3	NM_001025389.2	c.212C>A	p.Thr71Asn	missense_variant	Exon 2 of 15	ENST00000396553.7	NP_001020560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000396553.7	c.212C>A	p.Thr71Asn	missense_variant	Exon 2 of 15	1	NM_001025389.2	ENSP00000379801.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.212C>A (p.T71N) alteration is located in exon 2 (coding exon 1) of the AMPD3 gene. This alteration results from a C to A substitution at nucleotide position 212, causing the threonine (T) at amino acid position 71 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.24	.;.;.;T;.;T
Eigen	Benign	0.052
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;.;.;M;.;M
PhyloP100		3.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N
REVEL	Benign	0.085
Sift	Uncertain	0.020	D;T;D;T;T;T
Sift4G	Benign	0.080	T;T;T;T;T;T
Polyphen		0.41	.;.;.;B;.;B
Vest4		0.42, 0.42, 0.42, 0.40
MutPred		0.22		Loss of phosphorylation at T71 (P = 0.0148);.;Loss of phosphorylation at T71 (P = 0.0148);Loss of phosphorylation at T71 (P = 0.0148);.;Loss of phosphorylation at T71 (P = 0.0148);
MVP		0.62
MPC		0.35
ClinPred		0.56	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.34
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr11-10483278;