Genetic Variant NM_017553.3:c.3737G>A (chr15-40987186-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PP5_ModerateBP4

The NM_017553.3(INO80):c.3737G>A(p.Arg1246Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,602,126 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 Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

INO80
NM_017553.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.78

Publications

5 publications found

Variant links:

Genes affected

INO80 (HGNC:26956): (INO80 complex ATPase subunit) This gene encodes a subunit of the chromatin remodeling complex, which is classified into subfamilies depending on sequence features apart from the conserved ATPase domain. This protein is the catalytic ATPase subunit of the INO80 chromatin remodeling complex, which is characterized by a DNA-binding domain. This protein is proposed to bind DNA and be recruited by the YY1 transcription factor to activate certain genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

INO80 Gene-Disease associations (from GenCC):

immunodeficiency, common variable, 1
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

INO80 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PP5

Variant 15-40987186-C-T is Pathogenic according to our data. Variant chr15-40987186-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 183320.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.01975584). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80	NM_017553.3	MANE Select	c.3737G>A	p.Arg1246Gln	missense	Exon 31 of 36	NP_060023.1	Q9ULG1
	INO80	NR_104038.2		n.3960G>A		non_coding_transcript_exon	Exon 30 of 35

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INO80	ENST00000648947.1	MANE Select	c.3737G>A	p.Arg1246Gln	missense	Exon 31 of 36	ENSP00000497609.1	Q9ULG1
INO80	ENST00000558357.6	TSL:1	n.*294G>A		non_coding_transcript_exon	Exon 30 of 35	ENSP00000453677.1	H0YMN5
INO80	ENST00000558357.6	TSL:1	n.*294G>A		3_prime_UTR	Exon 30 of 35	ENSP00000453677.1	H0YMN5

Frequencies

GnomAD3 genomes

AF:

0.000785

AC:

119

AN:

151572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000567

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.000306

AC:

AN:

251224

AF XY:

0.000236

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000152

AC:

220

AN:

1450436

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

722404

show subpopulations

African (AFR)

AF:

0.00283

AC:

AN:

33208

American (AMR)

AF:

0.000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0000767

AC:

AN:

26082

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.000750

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000454

AC:

AN:

1101700

Other (OTH)

AF:

0.000350

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000784

AC:

119

AN:

151690

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.00254

AC:

105

AN:

41288

American (AMR)

AF:

0.000197

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.000567

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67876

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000233

Hom.:

Bravo

AF:

0.000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

INO80-related immunodeficiency (1)

Seizure;C2677180:Primary microcephaly;C3714756:Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.65

MutationAssessor

Benign

-0.36

PhyloP100

4.8

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.2

REVEL

Pathogenic

0.72

Sift

Uncertain

0.021

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.30

MVP

0.31

MPC

0.46

ClinPred

0.070

GERP RS

4.3

Varity_R

0.40

gMVP

0.79

Mutation Taster

=9/91

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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