15-40980290-C-T

Variant names:

• chr15-40980290-C-T
• rs775509728
• NM_017553.3:c.4604G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017553.3(INO80):​c.4604G>A​(p.Ser1535Asn) 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. 13/21 in silico tools predict 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. S1535I) 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: 2.29

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]

LOC124903476 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118091464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80	NM_017553.3	c.4604G>A	p.Ser1535Asn	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.4604G>A	p.Ser1535Asn	missense_variant	Exon 36 of 36		NM_017553.3	ENSP00000497609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T;T
Eigen	Benign	-0.035
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	.;.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.68	.;N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.28	.;T;T
Polyphen		0.18	B;B;B
Vest4		0.081, 0.10
MutPred		0.11		Loss of phosphorylation at S1535 (P = 0.0388);Loss of phosphorylation at S1535 (P = 0.0388);Loss of phosphorylation at S1535 (P = 0.0388);
MVP		0.21
MPC		0.39
ClinPred		0.38	T
GERP RS		5.4
Varity_R		0.49
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs775509728; hg19: chr15-41272488;