Variant chr16-30001490-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173618.3(INO80E):c.473C>A(p.Pro158His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,613,312 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

INO80E
NM_173618.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89

Variant links:

Genes affected

INO80E (HGNC:26905): (INO80 complex subunit E) Predicted to be involved in DNA recombination; DNA repair; and chromatin remodeling. Located in nucleolus and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

INO80E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024632514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INO80E	NM_173618.3 linkuse as main transcript	c.473C>A	p.Pro158His	missense_variant	6/7	ENST00000563197.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INO80E	ENST00000563197.6 linkuse as main transcript	c.473C>A	p.Pro158His	missense_variant	6/7	1	NM_173618.3	P3	Q8NBZ0-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000410

AC:

101

AN:

246534

Hom.:

AF XY:

0.000320

AC XY:

AN XY:

134210

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.000595

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.000333

AC:

487

AN:

1461094

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00130

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000256

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000523

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.473C>A (p.P158H) alteration is located in exon 6 (coding exon 6) of the INO80E gene. This alteration results from a C to A substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 to be replaced by a histidine (H). 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

0.21

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.080

N;.;N

Sift

Uncertain

0.010

D;.;D

Sift4G

Uncertain

0.010

D;D;T

Polyphen

0.99

D;.;.

Vest4

0.48

MVP

0.78

MPC

0.69

ClinPred

0.078

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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