NM_000022.4:c.1079-18C>T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000022.4(ADA):c.1079-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,014 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ADA
NM_000022.4 intron
NM_000022.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.843
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 20-44619865-G-A is Benign according to our data. Variant chr20-44619865-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1440624.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADA | NM_000022.4 | c.1079-18C>T | intron_variant | Intron 11 of 11 | ENST00000372874.9 | NP_000013.2 | ||
ADA | NM_001322051.2 | c.1007-18C>T | intron_variant | Intron 10 of 10 | NP_001308980.1 | |||
ADA | NM_001322050.2 | c.674-18C>T | intron_variant | Intron 10 of 10 | NP_001308979.1 | |||
ADA | NR_136160.2 | n.1106-18C>T | intron_variant | Intron 10 of 10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADA | ENST00000372874.9 | c.1079-18C>T | intron_variant | Intron 11 of 11 | 1 | NM_000022.4 | ENSP00000361965.4 | |||
ADA | ENST00000695995.1 | c.689-18C>T | intron_variant | Intron 8 of 8 | ENSP00000512318.1 | |||||
ADA | ENST00000695991.1 | c.617-18C>T | intron_variant | Intron 7 of 7 | ENSP00000512314.1 | |||||
ADA | ENST00000695956.1 | c.233-5C>T | splice_region_variant, intron_variant | Intron 2 of 2 | ENSP00000512285.1 | |||||
ADA | ENST00000696038.1 | n.*1269C>T | non_coding_transcript_exon_variant | Exon 9 of 9 | ENSP00000512344.1 | |||||
ADA | ENST00000696038.1 | n.*1269C>T | 3_prime_UTR_variant | Exon 9 of 9 | ENSP00000512344.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250528Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135500
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461842Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727222
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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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
Dec 30, 2023
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