20-44620135-C-T

Variant names:

• chr20-44620135-C-T
• rs536271022
• NM_000022.4:c.1078+164G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000022.4(ADA):​c.1078+164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 152,302 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 0.0012 (0 hom., cov: 32)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-44620135-C-T is Benign according to our data. Variant chr20-44620135-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770779.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.1078+164G>A		intron_variant	Intron 11 of 11	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.1006+164G>A		intron_variant	Intron 10 of 10		NP_001308980.1
ADA	NM_001322050.2	c.673+164G>A		intron_variant	Intron 10 of 10		NP_001308979.1
ADA	NR_136160.2	n.1105+164G>A		intron_variant	Intron 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.1078+164G>A		intron_variant	Intron 11 of 11	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.688+164G>A		intron_variant	Intron 8 of 8			ENSP00000512318.1
ADA	ENST00000695991.1	c.616+164G>A		intron_variant	Intron 7 of 7			ENSP00000512314.1
ADA	ENST00000695956.1	c.232+164G>A		intron_variant	Intron 2 of 2			ENSP00000512285.1
ADA	ENST00000696038.1	n.*999G>A		non_coding_transcript_exon_variant	Exon 9 of 9			ENSP00000512344.1
ADA	ENST00000696038.1	n.*999G>A		3_prime_UTR_variant	Exon 9 of 9			ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74484

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000900 Hom.: 0

Bravo AF: 0.000684

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ADA: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs536271022; hg19: chr20-43248776;