15-40980401-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017553.3(INO80):c.4493G>A(p.Arg1498Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,461,450 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1498P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

INO80
NM_017553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07

Publications

0 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:

LOC124903476 (HGNC:):

LOC124903476 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80	NM_017553.3 link	c.4493G>A	p.Arg1498Gln	missense_variant	Exon 36 of 36	ENST00000648947.1	NP_060023.1	Q9ULG1A0A024R9R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1 link	c.4493G>A	p.Arg1498Gln	missense_variant	Exon 36 of 36		NM_017553.3	ENSP00000497609.1		Q9ULG1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

249978

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5484

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111980

Other (OTH)

AF:

0.0000331

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4493G>A (p.R1498Q) alteration is located in exon 36 (coding exon 35) of the INO80 gene. This alteration results from a G to A substitution at nucleotide position 4493, causing the arginine (R) at amino acid position 1498 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.048

T;T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

0.97

L;L;L

PhyloP100

6.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.84

.;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.052

.;T;T

Sift4G

Benign

0.23

.;T;T

Polyphen

0.99

D;D;D

Vest4

0.77, 0.77

MutPred

0.19

Loss of methylation at R1498 (P = 0.0656);Loss of methylation at R1498 (P = 0.0656);Loss of methylation at R1498 (P = 0.0656);

MVP

0.65

MPC

1.2

ClinPred

0.29

GERP RS

5.4

Varity_R

0.26

gMVP

0.48

Mutation Taster

=61/39

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

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15-40980401-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over