rs769506264
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000022.4(ADA):c.525G>A(p.Gln175Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
ADA
NM_000022.4 synonymous
NM_000022.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0230
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]
PKIG (HGNC:9019): (cAMP-dependent protein kinase inhibitor gamma) This gene encodes a member of the protein kinase inhibitor family. Studies of a similar protein in mice suggest that this protein acts as a potent competitive cAMP-dependent protein kinase inhibitor, and is a predominant form of inhibitor in various tissues. The encoded protein may be involved in osteogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 20-44624283-C-T is Benign according to our data. Variant chr20-44624283-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 536188.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.023 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ADA | NM_000022.4 | c.525G>A | p.Gln175Gln | synonymous_variant | Exon 6 of 12 | ENST00000372874.9 | NP_000013.2 | |
| ADA | NM_001322051.2 | c.525G>A | p.Gln175Gln | synonymous_variant | Exon 6 of 11 | NP_001308980.1 | ||
| ADA | NM_001322050.2 | c.120G>A | p.Gln40Gln | synonymous_variant | Exon 5 of 11 | NP_001308979.1 | ||
| ADA | NR_136160.2 | n.617G>A | non_coding_transcript_exon_variant | Exon 6 of 11 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ADA | ENST00000372874.9 | c.525G>A | p.Gln175Gln | synonymous_variant | Exon 6 of 12 | 1 | NM_000022.4 | ENSP00000361965.4 | ||
| ADA | ENST00000695995.1 | c.217-1205G>A | intron_variant | Intron 3 of 8 | ENSP00000512318.1 | |||||
| ADA | ENST00000695991.1 | c.217-1353G>A | intron_variant | Intron 3 of 7 | ENSP00000512314.1 | |||||
| ADA | ENST00000696038.1 | n.*271G>A | non_coding_transcript_exon_variant | Exon 6 of 9 | ENSP00000512344.1 | |||||
| ADA | ENST00000696038.1 | n.*271G>A | 3_prime_UTR_variant | Exon 6 of 9 | ENSP00000512344.1 |
Frequencies
GnomAD3 genomes 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251388Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135880
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461732Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727168
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GnomAD4 genome 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency Benign:1
Jul 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at