15-40980317-C-A

Variant names:

• chr15-40980317-C-A
• rs763157145
• NM_017553.3:c.4577G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017553.3(INO80):​c.4577G>T​(p.Gly1526Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. G1526E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INO80 NM_017553.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 1 publications found

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

LOC124903476 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.420469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80	NM_017553.3	c.4577G>T	p.Gly1526Val	missense_variant	Exon 36 of 36	ENST00000648947.1	NP_060023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1	c.4577G>T	p.Gly1526Val	missense_variant	Exon 36 of 36		NM_017553.3	ENSP00000497609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	.;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	0.34	N;N;N
PhyloP100		2.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	.;N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0090	.;D;D
Sift4G	Uncertain	0.014	.;D;D
Polyphen		1.0	D;D;D
Vest4		0.16, 0.17
MutPred		0.15		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);
MVP		0.70
MPC		1.2
ClinPred		0.83	D
GERP RS		5.4
Varity_R		0.25
gMVP		0.57
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs763157145; hg19: chr15-41272515;