15-40983060-T-C

Variant names:

• chr15-40983060-T-C
• rs1566897746
• NM_017553.3:c.4255A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017553.3(INO80):​c.4255A>G​(p.Met1419Val) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INO80 NM_017553.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.915
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050342172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017553.3. 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
	INO80	NM_017553.3	MANE Select	c.4255A>G	p.Met1419Val	missense	Exon 35 of 36	NP_060023.1	Q9ULG1
	INO80	NR_104038.2		n.4478A>G		non_coding_transcript_exon	Exon 34 of 35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80	ENST00000648947.1	MANE Select	c.4255A>G	p.Met1419Val	missense	Exon 35 of 36	ENSP00000497609.1	Q9ULG1
	INO80	ENST00000558357.6	TSL:1	n.*812A>G		non_coding_transcript_exon	Exon 34 of 35	ENSP00000453677.1	H0YMN5
	INO80	ENST00000558357.6	TSL:1	n.*812A>G		3_prime_UTR	Exon 34 of 35	ENSP00000453677.1	H0YMN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.92
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.22
Sift	Benign	1.0	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.28		Gain of sheet (P = 0.0043)
MVP		0.20
MPC		0.34
ClinPred		0.067	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.17

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

Other links and lift over

dbSNP: rs1566897746; hg19: chr15-41275258;