rs73598374

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000372874.9(ADA):​c.22G>T​(p.Asp8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. D8N) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADA
ENST00000372874.9 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.538
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3410142).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADANM_000022.4 linkuse as main transcriptc.22G>T p.Asp8Tyr missense_variant 1/12 ENST00000372874.9 NP_000013.2
ADANM_001322051.2 linkuse as main transcriptc.22G>T p.Asp8Tyr missense_variant 1/11 NP_001308980.1
ADANM_001322050.2 linkuse as main transcriptc.-268G>T 5_prime_UTR_variant 1/11 NP_001308979.1
ADANR_136160.2 linkuse as main transcriptn.114G>T non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAENST00000372874.9 linkuse as main transcriptc.22G>T p.Asp8Tyr missense_variant 1/121 NM_000022.4 ENSP00000361965 P4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000713
AC:
1
AN:
140254
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
77720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1388788
Hom.:
0
Cov.:
32
AF XY:
0.00000146
AC XY:
1
AN XY:
686854
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.79
D;T
Eigen
Benign
-0.057
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.84
T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.34
T;T
MetaSVM
Uncertain
0.39
D
MutationAssessor
Benign
1.5
L;.
MutationTaster
Benign
0.73
D;D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Uncertain
0.57
Sift
Uncertain
0.010
D;D
Sift4G
Benign
0.061
T;T
Polyphen
0.92
P;.
Vest4
0.41
MutPred
0.45
Loss of disorder (P = 0.0194);Loss of disorder (P = 0.0194);
MVP
0.99
MPC
0.56
ClinPred
0.62
D
GERP RS
-1.4
Varity_R
0.63
gMVP
0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73598374; hg19: chr20-43280227; API