rs151336936

Positions:

chr20-44629155-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_000022.4(ADA):c.110C>T(p.Ala37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ADA
NM_000022.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

Variant links:

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]

ADA links:

ADA (HGNC:):

ADA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012588382).

BP6

Variant 20-44629155-G-A is Benign according to our data. Variant chr20-44629155-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 513280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00137 (208/152320) while in subpopulation AFR AF= 0.00493 (205/41580). AF 95% confidence interval is 0.00438. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADA	NM_000022.4 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	3/12	ENST00000372874.9	NP_000013.2	P00813A0A0S2Z381
ADA	NM_001322051.2 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	3/11		NP_001308980.1	F5GWI4
ADA	NM_001322050.2 linkuse as main transcript	c.-180C>T		5_prime_UTR_variant	3/11		NP_001308979.1
ADA	NR_136160.2 linkuse as main transcript	n.202C>T		non_coding_transcript_exon_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADA	ENST00000372874.9 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	3/12	1	NM_000022.4	ENSP00000361965.4	P00813
ADA	ENST00000695995.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	3/9			ENSP00000512318.1	A0A8Q3SI64
ADA	ENST00000695991.1 linkuse as main transcript	c.110C>T	p.Ala37Val	missense_variant	3/8			ENSP00000512314.1	A0A0S2Z3B9
ADA	ENST00000696038.1 linkuse as main transcript	n.110C>T		non_coding_transcript_exon_variant	3/9			ENSP00000512344.1	A0A8Q3SJ57

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000406

AC:

102

AN:

251326

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

188

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00490

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.00137

AC:

208

AN:

152320

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000544

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.79

D;D

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.013

T;T

MetaSVM

Uncertain

-0.077

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.24

Sift

Benign

0.27

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.0030

B;.

Vest4

0.36

MVP

0.67

MPC

0.15

ClinPred

0.013

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over