Genetic Variant NM_006869.4:c.392A>G (chr7-905169-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006869.4(ADAP1):c.392A>G(p.Tyr131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,610,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

ADAP1
NM_006869.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Publications

1 publications found

Variant links:

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADAP1 links:

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

COX19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3985751).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006869.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP1	NM_006869.4	MANE Select	c.392A>G	p.Tyr131Cys	missense	Exon 5 of 11	NP_006860.2	O75689-1
ADAP1	NM_001284308.2		c.425A>G	p.Tyr142Cys	missense	Exon 5 of 11	NP_001271237.2	O75689-2
ADAP1	NM_001284309.2		c.176A>G	p.Tyr59Cys	missense	Exon 5 of 11	NP_001271238.2	O75689-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAP1	ENST00000265846.10	TSL:1 MANE Select	c.392A>G	p.Tyr131Cys	missense	Exon 5 of 11	ENSP00000265846.5	O75689-1
ADAP1	ENST00000539900.5	TSL:2	c.425A>G	p.Tyr142Cys	missense	Exon 5 of 11	ENSP00000442682.1	O75689-2
ADAP1	ENST00000943017.1		c.392A>G	p.Tyr131Cys	missense	Exon 5 of 11	ENSP00000613076.1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

248362

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000795

AC:

116

AN:

1458500

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

725622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000103

AC:

114

AN:

1111080

Other (OTH)

AF:

0.0000332

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151636

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41182

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000456

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000415

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

0.22

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.021

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

PhyloP100

2.5

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.25

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.89

MutPred

0.36

Loss of phosphorylation at Y131 (P = 0.0553)

MVP

0.37

MPC

1.2

ClinPred

0.78

GERP RS

4.0

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.64

Mutation Taster

=46/54

disease causing

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over