chr11-10461524-C-T

Variant names:

• chr11-10461524-C-T
• rs145604316
• NM_001025389.2:c.5C>T

Variant summary

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

The NM_001172431.2(AMPD3):​c.-268C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: AMPD3 NM_001172431.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50
• Publications: 6 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172431.2. 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
	AMPD3	NM_001025389.2	MANE Select	c.5C>T	p.Pro2Leu	missense	Exon 2 of 15	NP_001020560.1	Q01432-1
	AMPD3	NM_001172431.2		c.-268C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001165902.1	Q01432-6
	AMPD3	NM_000480.3		c.32C>T	p.Pro11Leu	missense	Exon 2 of 15	NP_000471.1	Q01432-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000396553.7	TSL:1 MANE Select	c.5C>T	p.Pro2Leu	missense	Exon 2 of 15	ENSP00000379801.2	Q01432-1
	AMPD3	ENST00000396554.7	TSL:1	c.32C>T	p.Pro11Leu	missense	Exon 2 of 15	ENSP00000379802.3	Q01432-4
	AMPD3	ENST00000524866.5	TSL:1	c.5C>T	p.Pro2Leu	missense	Exon 3 of 6	ENSP00000433284.1	E9PLK6

Frequencies

GnomAD3 genomes AF: 0.000224 AC: 34 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000247 AC: 62 AN: 251130 AF XY: 0.000206

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000283 AC: 414 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.000275 AC XY: 200 AN XY: 727230

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.000447 AC: 20 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86242

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000328 AC: 365 AN: 1112006

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74438

African (AFR) AF: 0.000145 AC: 6 AN: 41512

American (AMR) AF: 0.000458 AC: 7 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000223 Hom.: 0

Bravo AF: 0.000223

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000699 AC: 6

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.91
MPC		0.86
ClinPred		0.62	D
GERP RS		5.7
PromoterAI		-0.045	Neutral
Varity_R		0.38
gMVP		0.44
Mutation Taster		=138/162	disease causing

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

dbSNP: rs145604316; hg19: chr11-10483071; COSMIC: COSV67331294;