rs4910118

Variant names:

• chr11-10308138-C-T
• rs4910118
• ENST00000527261.5:n.-175C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000527261.5(AMPD3):​n.-175C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,290 control chromosomes in the GnomAD database, including 408 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 0.039 (408 hom., cov: 32)
• Consequence: AMPD3 ENST00000527261.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.-175C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000527261.5	n.-175C>T		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5911 AN: 152176 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0388 AC: 5913 AN: 152290 Hom.: 408 Cov.: 32 AF XY: 0.0417 AC XY: 3107 AN XY: 74470

African (AFR) AF: 0.0299 AC: 1241 AN: 41560

American (AMR) AF: 0.135 AC: 2063 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5164

South Asian (SAS) AF: 0.0867 AC: 419 AN: 4832

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0103 AC: 704 AN: 68022

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0274 Hom.: 37

Bravo AF: 0.0532

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		-0.015

Splicing

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

Other links and lift over

dbSNP: rs4910118; hg19: chr11-10329685;