3-49256817-C-G

Variant names:

• chr3-49256817-C-G
• NM_001135197.2:c.1320C>G
• IHO1 p.Asp440Glu

Variant summary

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

The NM_001135197.2(IHO1):​c.1320C>G​(p.Asp440Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IHO1 NM_001135197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 0 publications found

Genes affected

IHO1 (HGNC:27945): (interactor of HORMAD1 1) Predicted to be involved in gamete generation; meiosis I cell cycle process; and regulation of homologous chromosome segregation. Predicted to be active in condensed nuclear chromosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.030504227).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135197.2. 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
	IHO1	NM_001135197.2	MANE Select	c.1320C>G	p.Asp440Glu	missense	Exon 8 of 8	NP_001128669.1	Q8IYA8-1
	IHO1	NM_178173.4		c.1320C>G	p.Asp440Glu	missense	Exon 10 of 10	NP_835467.2	Q8IYA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IHO1	ENST00000452691.7	TSL:2 MANE Select	c.1320C>G	p.Asp440Glu	missense	Exon 8 of 8	ENSP00000407837.2	Q8IYA8-1
	IHO1	ENST00000296449.9	TSL:1	c.1320C>G	p.Asp440Glu	missense	Exon 10 of 10	ENSP00000296449.5	Q8IYA8-1
	IHO1	ENST00000438782.5	TSL:5	c.1320C>G	p.Asp440Glu	missense	Exon 8 of 8	ENSP00000391788.1	Q8IYA8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.24
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.054
Sift	Benign	0.12	T
Sift4G	Uncertain	0.044	D
Varity_R		0.045
gMVP		0.018
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-49294250;