Variant chr4-122396278-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_139243.4(ADAD1):c.625A>G(p.Ile209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,443,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ADAD1
NM_139243.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.685

Variant links:

Genes affected

ADAD1 (HGNC:30713): (adenosine deaminase domain containing 1) Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing and adenosine to inosine editing. Predicted to act upstream of or within spermatid development. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ADAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11339691).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAD1	NM_139243.4 linkuse as main transcript	c.625A>G	p.Ile209Val	missense_variant	7/13	ENST00000296513.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAD1	ENST00000296513.7 linkuse as main transcript	c.625A>G	p.Ile209Val	missense_variant	7/13	2	NM_139243.4	P1	Q96M93-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

235720

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000377

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1443126

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000735

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.625A>G (p.I209V) alteration is located in exon 7 (coding exon 5) of the ADAD1 gene. This alteration results from a A to G substitution at nucleotide position 625, causing the isoleucine (I) at amino acid position 209 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;L;.

MutationTaster

Benign

0.91

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.25

N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.70

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.017

B;.;B;.

Vest4

0.23

MutPred

0.54

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);.;

MVP

0.18

MPC

0.11

ClinPred

0.19

GERP RS

4.8

Varity_R

0.065

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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