18-35480527-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.595
Variant links:
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]

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ACMG classification

Classification made for transcript

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
INO80CNM_194281.4 linkc.193G>T p.Val65Leu missense_variant Exon 2 of 5 ENST00000334598.12 NP_919257.2 Q6PI98-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INO80CENST00000334598.12 linkc.193G>T p.Val65Leu missense_variant Exon 2 of 5 1 NM_194281.4 ENSP00000334473.6 Q6PI98-1
ENSG00000267140ENST00000589258.1 linkc.156+17192G>T intron_variant Intron 1 of 2 3 ENSP00000467041.1 K7ENP7

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
LINK: link

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; API