Genetic Variant INO80C:p.Arg23Lys (chr18-35497807-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194281.4(INO80C):c.68G>A(p.Arg23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,750 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

INO80C
NM_194281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Publications

0 publications found

Variant links:

Genes affected

INO80C (HGNC:26994): (INO80 complex subunit C) Predicted to be involved in chromatin remodeling. Part of Ino80 complex and MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

INO80C links:

ENSG00000267140 (HGNC:):

ENSG00000267140 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22018728).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INO80C	NM_194281.4	MANE Select	c.68G>A	p.Arg23Lys	missense	Exon 1 of 5	NP_919257.2
INO80C	NM_001098817.2		c.68G>A	p.Arg23Lys	missense	Exon 1 of 7	NP_001092287.1	Q6PI98-4
INO80C	NM_001308064.2		c.-311G>A		upstream_gene	N/A	NP_001294993.1	K7EIY8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INO80C	ENST00000334598.12	TSL:1 MANE Select	c.68G>A	p.Arg23Lys	missense	Exon 1 of 5	ENSP00000334473.6	Q6PI98-1
ENSG00000267140	ENST00000589258.1	TSL:3	c.68G>A	p.Arg23Lys	missense	Exon 1 of 3	ENSP00000467041.1	K7ENP7
INO80C	ENST00000441607.6	TSL:2	c.68G>A	p.Arg23Lys	missense	Exon 1 of 7	ENSP00000391457.1	Q6PI98-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

249148

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460492

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726586

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111364

Other (OTH)

AF:

0.0000166

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68056

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0098

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.84

M_CAP

Benign

0.0044

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.9

PhyloP100

3.2

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.57

MutPred

0.33

Gain of methylation at R23 (P = 0.0076)

MVP

0.35

MPC

0.0038

ClinPred

0.92

GERP RS

4.6

PromoterAI

0.091

Neutral

(source)

Varity_R

0.45

gMVP

0.50

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over