NM_194281.4:c.193G>T

Variant names:

• chr18-35480527-C-A
• NM_194281.4:c.193G>T

Variant summary

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

The NM_194281.4(INO80C):​c.193G>T​(p.Val65Leu) 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. 16/21 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: INO80C NM_194281.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.595
• Publications: 0 publications found

Genes affected

INO80C (HGNC:26994): (INO80 complex subunit C) Predicted to be involved in chromatin remodeling. Part of Ino80 complex and MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267140 (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=0.06713465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194281.4. 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
	INO80C	NM_194281.4	MANE Select	c.193G>T	p.Val65Leu	missense	Exon 2 of 5	NP_919257.2
	INO80C	NM_001098817.2		c.301G>T	p.Val101Leu	missense	Exon 4 of 7	NP_001092287.1	Q6PI98-4
	INO80C	NM_001308064.2		c.28G>T	p.Val10Leu	missense	Exon 2 of 5	NP_001294993.1	K7EIY8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80C	ENST00000334598.12	TSL:1 MANE Select	c.193G>T	p.Val65Leu	missense	Exon 2 of 5	ENSP00000334473.6	Q6PI98-1
	ENSG00000267140	ENST00000589258.1	TSL:3	c.156+17192G>T		intron	N/A	ENSP00000467041.1	K7ENP7
	INO80C	ENST00000441607.6	TSL:2	c.301G>T	p.Val101Leu	missense	Exon 4 of 7	ENSP00000391457.1	Q6PI98-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.59
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.056
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.11	B
Vest4		0.11
MutPred		0.049		Loss of glycosylation at S67 (P = 0.1869)
MVP		0.18
MPC		0.12
ClinPred		0.20	T
GERP RS		4.2
Varity_R		0.044
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr18-33060491;