rs11555566

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000022.4(ADA):​c.239A>T​(p.Lys80Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K80R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ADA
NM_000022.4 missense

Scores

6
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.06
Variant links:
Genes affected
ADA (HGNC:186): (adenosine deaminase) This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADANM_000022.4 linkc.239A>T p.Lys80Ile missense_variant Exon 4 of 12 ENST00000372874.9 NP_000013.2 P00813A0A0S2Z381
ADANM_001322051.2 linkc.239A>T p.Lys80Ile missense_variant Exon 4 of 11 NP_001308980.1 F5GWI4
ADANM_001322050.2 linkc.-51A>T 5_prime_UTR_variant Exon 4 of 11 NP_001308979.1
ADANR_136160.2 linkn.331A>T non_coding_transcript_exon_variant Exon 4 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAENST00000372874.9 linkc.239A>T p.Lys80Ile missense_variant Exon 4 of 12 1 NM_000022.4 ENSP00000361965.4 P00813
ADAENST00000695995.1 linkc.216+2470A>T intron_variant Intron 3 of 8 ENSP00000512318.1 A0A8Q3SI64
ADAENST00000695991.1 linkc.216+2470A>T intron_variant Intron 3 of 7 ENSP00000512314.1 A0A0S2Z3B9
ADAENST00000696038.1 linkn.237A>T non_coding_transcript_exon_variant Exon 4 of 9 ENSP00000512344.1 A0A8Q3SJ57

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.94
D;D
Eigen
Benign
-0.063
Eigen_PC
Benign
-0.012
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Uncertain
0.46
D
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Pathogenic
0.71
Sift
Uncertain
0.0050
D;D
Sift4G
Benign
0.073
T;T
Polyphen
0.11
B;.
Vest4
0.64
MutPred
0.70
Loss of methylation at K80 (P = 0.0143);Loss of methylation at K80 (P = 0.0143);
MVP
0.94
MPC
0.78
ClinPred
0.99
D
GERP RS
2.6
Varity_R
0.77
gMVP
0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-43255220; API