rs244076

Variant names:

• chr20-44624274-T-A
• rs244076
• NM_000022.4:c.534A>T

Your query was ambiguous. Multiple possible variants found:

• chr20-44624274-T-A
• chr20-44624274-T-C
• chr20-44624274-T-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000022.4(ADA):​c.534A>T​(p.Val178Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V178V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADA NM_000022.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-0.174 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA	NM_000022.4	c.534A>T	p.Val178Val	synonymous_variant	Exon 6 of 12	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.534A>T	p.Val178Val	synonymous_variant	Exon 6 of 11		NP_001308980.1
ADA	NM_001322050.2	c.129A>T	p.Val43Val	synonymous_variant	Exon 5 of 11		NP_001308979.1
ADA	NR_136160.2	n.626A>T		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.534A>T	p.Val178Val	synonymous_variant	Exon 6 of 12	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000696038.1	n.*280A>T		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000512344.1
ADA	ENST00000696038.1	n.*280A>T		3_prime_UTR_variant	Exon 6 of 9			ENSP00000512344.1
ADA	ENST00000695995.1	c.217-1196A>T		intron_variant	Intron 3 of 8			ENSP00000512318.1
ADA	ENST00000695991.1	c.217-1344A>T		intron_variant	Intron 3 of 7			ENSP00000512314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.4
DANN	Benign	0.85
PhyloP100		-0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs244076; hg19: chr20-43252915;