11-10360637-T-C

Variant names:

• chr11-10360637-T-C
• rs2957717
• ENST00000295663.9:n.50+29928T>C

Variant summary

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

The ENST00000295663.9(AMPD3):​n.50+29928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,452 control chromosomes in the GnomAD database, including 29,875 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 0.62 (29875 hom., cov: 28)
• Consequence: AMPD3 ENST00000295663.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 1 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.501+29928T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000295663.9	n.50+29928T>C		intron_variant	Intron 1 of 2	1
AMPD3	ENST00000527261.5	n.501+29928T>C		intron_variant	Intron 2 of 2	1
AMPD3	ENST00000532966.1	n.119+3246T>C		intron_variant	Intron 1 of 1	1
AMPD3	ENST00000532250.5	c.-6+29928T>C		intron_variant	Intron 2 of 3	4		ENSP00000432707.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93591 AN: 151336 Hom.: 29866 Cov.: 28

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.618 AC: 93623 AN: 151452 Hom.: 29875 Cov.: 28 AF XY: 0.613 AC XY: 45326 AN XY: 73934

African (AFR) AF: 0.543 AC: 22404 AN: 41236

American (AMR) AF: 0.528 AC: 8043 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2376 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1040 AN: 5156

South Asian (SAS) AF: 0.571 AC: 2736 AN: 4788

European-Finnish (FIN) AF: 0.708 AC: 7385 AN: 10432

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47506 AN: 67842

Other (OTH) AF: 0.613 AC: 1283 AN: 2094

Alfa AF: 0.643 Hom.: 3950

Bravo AF: 0.597

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs2957717; hg19: chr11-10382184;