rs2071019

Variant names:

• chr11-10455151-C-T
• rs2071019
• ENST00000396554.7:c.22+4108C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The NM_000480.3(AMPD3):​c.22+4108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 985,268 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (505 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1789 hom.)
• Consequence: AMPD3 NM_000480.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 11-10455151-C-T is Benign according to our data. Variant chr11-10455151-C-T is described in ClinVar as Benign. ClinVar VariationId is 302138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000480.3. 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_000480.3		c.22+4108C>T		intron	N/A	NP_000471.1	Q01432-4
	AMPD3	NM_001172431.2		c.-278+4636C>T		intron	N/A	NP_001165902.1	Q01432-6
	AMPD3	NM_001025389.2	MANE Select	c.-303C>T		upstream_gene	N/A	NP_001020560.1	Q01432-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD3	ENST00000396554.7	TSL:1	c.22+4108C>T		intron	N/A	ENSP00000379802.3	Q01432-4
	AMPD3	ENST00000524866.5	TSL:1	c.-114-189C>T		intron	N/A	ENSP00000433284.1	E9PLK6
	AMPD3	ENST00000534047.5	TSL:1	n.22+4108C>T		intron	N/A	ENSP00000433937.1	E9PIR5

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10875 AN: 152094 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0780

GnomAD4 exome AF: 0.0589 AC: 49070 AN: 833056 Hom.: 1789 Cov.: 32 AF XY: 0.0595 AC XY: 22905 AN XY: 384692

African (AFR) AF: 0.0900 AC: 1420 AN: 15784

American (AMR) AF: 0.0579 AC: 57 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 662 AN: 5152

East Asian (EAS) AF: 0.100 AC: 363 AN: 3628

South Asian (SAS) AF: 0.218 AC: 3584 AN: 16458

European-Finnish (FIN) AF: 0.0290 AC: 8 AN: 276

Middle Eastern (MID) AF: 0.0975 AC: 158 AN: 1620

European-Non Finnish (NFE) AF: 0.0534 AC: 40704 AN: 761856

Other (OTH) AF: 0.0774 AC: 2114 AN: 27298

GnomAD4 genome AF: 0.0716 AC: 10902 AN: 152212 Hom.: 505 Cov.: 32 AF XY: 0.0731 AC XY: 5444 AN XY: 74432

African (AFR) AF: 0.0864 AC: 3586 AN: 41506

American (AMR) AF: 0.0618 AC: 945 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3472

East Asian (EAS) AF: 0.111 AC: 576 AN: 5180

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4814

European-Finnish (FIN) AF: 0.0326 AC: 346 AN: 10608

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0543 AC: 3691 AN: 68026

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0649 Hom.: 144

Bravo AF: 0.0712

Asia WGS AF: 0.194 AC: 672 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Erythrocyte AMP deaminase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		1.1
PromoterAI		-0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2071019; hg19: chr11-10476698;