chr15-40982960-G-A

Variant names:

• chr15-40982960-G-A
• rs772084393
• NM_017553.3:c.4355C>T

Variant summary

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

The NM_017553.3(INO80):​c.4355C>T​(p.Ser1452Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INO80 NM_017553.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80	NM_017553.3	c.4355C>T	p.Ser1452Phe	missense_variant	Exon 35 of 36	ENST00000648947.1	NP_060023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80	ENST00000648947.1	c.4355C>T	p.Ser1452Phe	missense_variant	Exon 35 of 36		NM_017553.3	ENSP00000497609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;.;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.016	.;D;D
Sift4G	Benign	0.70	.;T;T
Polyphen		0.99	D;D;D
Vest4		0.81, 0.87
MutPred		0.22		Loss of phosphorylation at S1452 (P = 0.0026);Loss of phosphorylation at S1452 (P = 0.0026);Loss of phosphorylation at S1452 (P = 0.0026);
MVP		0.83
MPC		1.1
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.28
gMVP		0.49

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: rs772084393; hg19: chr15-41275158; COSMIC: COSV104678801; COSMIC: COSV104678801;