rs199722402

Positions:

chr15-40987186-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP2PP5BP4BS2_Supporting

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 (no stars).

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 no assertion criteria provided P:1

Conservation

PhyloP100: 4.78

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), INO80. . Trascript score misZ 3.7589 (greater than threshold 3.09). GenCC has associacion of gene with immunodeficiency, common variable, 1.

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 id is 183320.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr15-40987186-C-T is described in Lovd as [Likely_pathogenic].

BP4

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

BS2

High AC in GnomAd4 at 119 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INO80	NM_017553.3 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant	31/36	ENST00000648947.1	NP_060023.1
INO80	XM_047432698.1 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant	31/36		XP_047288654.1
INO80	XM_011521686.4 linkuse as main transcript	c.1787G>A	p.Arg596Gln	missense_variant	17/22		XP_011519988.1
INO80	NR_104038.2 linkuse as main transcript	n.3960G>A		non_coding_transcript_exon_variant	30/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant	31/36		NM_017553.3	ENSP00000497609	P1

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

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251224

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135804

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 SAS 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

Gnomad4 AFR exome

AF:

0.00283

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000784

AC:

119

AN:

151690

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.00254

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000567

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000186

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Seizure;C2677180:Primary microcephaly;C3714756:Intellectual disability

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.075

T;T;T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

.;.;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.020

T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

-0.36

N;N;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-2.2

.;N;N;.

REVEL

Pathogenic

0.72

Sift

Uncertain

0.021

.;D;D;.

Sift4G

Uncertain

0.010

.;D;D;D

Polyphen

0.99

D;D;D;.

Vest4

0.30, 0.30

MVP

0.31

MPC

0.46

ClinPred

0.070

GERP RS

4.3

Varity_R

0.40

gMVP

0.79

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

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