Genetic Variant INO80B:p.Met272Lys (chr2-74457608-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_031288.4(INO80B):c.815T>A(p.Met272Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,412,326 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M272R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

INO80B
NM_031288.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

Genes affected

INO80B (HGNC:13324): (INO80 complex subunit B) This gene encodes a subunit of an ATP-dependent chromatin remodeling complex, INO80, which plays a role in DNA and nucleosome-activated ATPase activity and ATP-dependent nucleosome sliding. Readthrough transcription of this gene into the neighboring downstream gene, which encodes WW domain-binding protein 1, generates a non-coding transcript. [provided by RefSeq, Feb 2011]

INO80B links:

INO80B-WBP1 (HGNC:49199): (INO80B-WBP1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring INO80B (INO80 complex subunit B) and WBP1 (WW domain-binding protein 1) genes on chromosome 2. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

INO80B-WBP1 links:

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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;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031288.4. 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
	INO80B	NM_031288.4	MANE Select	c.815T>A	p.Met272Lys	missense	Exon 5 of 5	NP_112578.2	Q9C086
	INO80B-WBP1	NR_037849.1		n.909T>A		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INO80B	ENST00000233331.12	TSL:1 MANE Select	c.815T>A	p.Met272Lys	missense	Exon 5 of 5	ENSP00000233331.7	Q9C086
INO80B-WBP1	ENST00000452361.5	TSL:2	n.815T>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000388677.1	J3KQ70
INO80B	ENST00000409917.5	TSL:2	c.*172T>A		3_prime_UTR	Exon 5 of 5	ENSP00000387267.1	B8ZZ93

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000283

AC:

AN:

1412326

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

700146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31526

American (AMR)

AF:

0.00

AC:

AN:

39670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24868

East Asian (EAS)

AF:

0.00

AC:

AN:

37238

South Asian (SAS)

AF:

0.0000366

AC:

AN:

82016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4614

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093582

Other (OTH)

AF:

0.00

AC:

AN:

58576

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.076

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.68

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.79

PhyloP100

3.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Benign

0.32

Sift4G

Benign

0.30

Polyphen

0.0010

Vest4

0.77

MutPred

0.53

Gain of sheet (P = 0.0221)

MVP

0.75

MPC

1.2

ClinPred

0.65

GERP RS

3.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.90

gMVP

0.75

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: 1

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