rs560858565

Variant names:

• chr20-44619682-G-A
• rs560858565
• NM_000022.4:c.*152C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-44619682-G-A
• chr20-44619682-G-C
• chr20-44619682-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_000022.4(ADA):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,002,394 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: ADA NM_000022.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000158 (24/152356) while in subpopulation SAS AF = 0.00435 (21/4828). AF 95% confidence interval is 0.00291. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA	NM_000022.4	MANE Select	c.*152C>T		3_prime_UTR	Exon 12 of 12	NP_000013.2
	ADA	NM_001322051.2		c.*152C>T		3_prime_UTR	Exon 11 of 11	NP_001308980.1	F5GWI4
	ADA	NM_001322050.2		c.*152C>T		3_prime_UTR	Exon 11 of 11	NP_001308979.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA	ENST00000372874.9	TSL:1 MANE Select	c.*152C>T		3_prime_UTR	Exon 12 of 12	ENSP00000361965.4	P00813
	ADA	ENST00000537820.2	TSL:1	c.*152C>T		3_prime_UTR	Exon 11 of 11	ENSP00000441818.1	F5GWI4
	ADA	ENST00000695995.1		c.*152C>T		3_prime_UTR	Exon 9 of 9	ENSP00000512318.1	A0A8Q3SI64

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000229 AC: 195 AN: 850038 Hom.: 2 Cov.: 11 AF XY: 0.000337 AC XY: 149 AN XY: 441874

African (AFR) AF: 0.0000937 AC: 2 AN: 21342

American (AMR) AF: 0.0000534 AC: 2 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21212

East Asian (EAS) AF: 0.00 AC: 0 AN: 34528

South Asian (SAS) AF: 0.00259 AC: 181 AN: 69966

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49184

Middle Eastern (MID) AF: 0.000221 AC: 1 AN: 4530

European-Non Finnish (NFE) AF: 0.00000350 AC: 2 AN: 572068

Other (OTH) AF: 0.000151 AC: 6 AN: 39766

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.52
DANN	Benign	0.82
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs560858565; hg19: chr20-43248323; COSMIC: COSV63068903; COSMIC: COSV63068903;