18-35480527-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/20 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06713465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80C	NM_194281.4	c.193G>T	p.Val65Leu	missense_variant	Exon 2 of 5	ENST00000334598.12	NP_919257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80C	ENST00000334598.12	c.193G>T	p.Val65Leu	missense_variant	Exon 2 of 5	1	NM_194281.4	ENSP00000334473.6
ENSG00000267140	ENST00000589258.1	c.156+17192G>T		intron_variant	Intron 1 of 2	3		ENSP00000467041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.301G>T (p.V101L) alteration is located in exon 4 (coding exon 4) of the INO80C gene. This alteration results from a G to T substitution at nucleotide position 301, causing the valine (V) at amino acid position 101 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.83	.;N;N;.;.
REVEL	Benign	0.056
Sift	Benign	0.14	.;T;T;.;.
Sift4G	Benign	0.21	T;T;T;T;.
Polyphen		0.11	B;B;.;.;.
Vest4		0.11
MutPred		0.049		Loss of glycosylation at S67 (P = 0.1869);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-33060491;