Genetic Variant NM_139243.4:c.187C>T (chr4-122381006-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139243.4(ADAD1):c.187C>T(p.Pro63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,440,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000014 ( 0 hom. )

Consequence

ADAD1
NM_139243.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.703

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11023858).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139243.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAD1	NM_139243.4	MANE Select	c.187C>T	p.Pro63Ser	missense	Exon 4 of 13	NP_640336.1	Q96M93-1
ADAD1	NM_001159285.2		c.187C>T	p.Pro63Ser	missense	Exon 3 of 12	NP_001152757.1	A0A140VKH5
ADAD1	NM_001159295.2		c.133C>T	p.Pro45Ser	missense	Exon 3 of 12	NP_001152767.1	Q96M93-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAD1	ENST00000296513.7	TSL:2 MANE Select	c.187C>T	p.Pro63Ser	missense	Exon 4 of 13	ENSP00000296513.2	Q96M93-1
ADAD1	ENST00000388724.6	TSL:1	c.187C>T	p.Pro63Ser	missense	Exon 3 of 12	ENSP00000373376.2	Q96M93-2
ADAD1	ENST00000388725.2	TSL:2	c.133C>T	p.Pro45Ser	missense	Exon 3 of 12	ENSP00000373377.2	Q96M93-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31498

American (AMR)

AF:

0.00

AC:

AN:

37218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25536

East Asian (EAS)

AF:

0.00

AC:

AN:

38972

South Asian (SAS)

AF:

0.00

AC:

AN:

81094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107084

Other (OTH)

AF:

0.00

AC:

AN:

59574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.81

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.70

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.16

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.033

Polyphen

0.99

Vest4

0.44

MutPred

0.34

Loss of stability (P = 0.1584)

MVP

0.13

MPC

0.38

ClinPred

0.97

GERP RS

4.4

Varity_R

0.13

gMVP

0.58

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over