18-35480454-A-C

Variant names:

• chr18-35480454-A-C
• NM_194281.4:c.266T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_194281.4(INO80C):​c.266T>G​(p.Val89Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INO80C NM_194281.4 missense, splice_region
• Scores: Splicing: ADA: 0.7091
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2806534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80C	NM_194281.4	c.266T>G	p.Val89Gly	missense_variant, splice_region_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.266T>G	p.Val89Gly	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_194281.4	ENSP00000334473.6
ENSG00000267140	ENST00000589258.1	c.156+17265T>G		intron_variant	Intron 1 of 2	3		ENSP00000467041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.374T>G (p.V125G) alteration is located in exon 4 (coding exon 4) of the INO80C gene. This alteration results from a T to G substitution at nucleotide position 374, causing the valine (V) at amino acid position 125 to be replaced by a glycine (G). 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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.044	.;T;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.7	.;D;D;.
REVEL	Benign	0.093
Sift	Benign	0.093	.;T;D;.
Sift4G	Benign	0.17	T;T;T;T
Polyphen		1.0	D;B;.;.
Vest4		0.38
MutPred		0.30		Loss of stability (P = 0.0037);Loss of stability (P = 0.0037);.;.;
MVP		0.55
MPC		0.49
ClinPred		0.87	D
GERP RS		6.0
Varity_R		0.40
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.71
dbscSNV1_RF	Benign	0.59
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-33060418;