3-49241285-A-G

Position:

• chr3-49241285-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135197.2(IHO1):​c.291A>G​(p.Ile97Met) 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. 14/20 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: IHO1 NM_001135197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.851

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

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=0.040331453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHO1	NM_001135197.2	c.291A>G	p.Ile97Met	missense_variant	4/8	ENST00000452691.7	NP_001128669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IHO1	ENST00000452691.7	c.291A>G	p.Ile97Met	missense_variant	4/8	2	NM_001135197.2	ENSP00000407837.2
IHO1	ENST00000296449.9	c.291A>G	p.Ile97Met	missense_variant	6/10	1		ENSP00000296449.5
IHO1	ENST00000438782.5	c.291A>G	p.Ile97Met	missense_variant	4/8	5		ENSP00000391788.1
IHO1	ENST00000366429.2	c.291A>G	p.Ile97Met	missense_variant	4/5	2		ENSP00000403700.1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.291A>G (p.I97M) alteration is located in exon 6 (coding exon 3) of the CCDC36 gene. This alteration results from a A to G substitution at nucleotide position 291, causing the isoleucine (I) at amino acid position 97 to be replaced by a methionine (M). 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	0.078
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0089	T;T;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.57	.;T;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.055	T;T;T;T
Sift4G	Uncertain	0.033	D;D;D;T
Polyphen		0.22	B;B;B;B
Vest4		0.12
MutPred		0.17		Loss of catalytic residue at I97 (P = 0.0205);Loss of catalytic residue at I97 (P = 0.0205);Loss of catalytic residue at I97 (P = 0.0205);Loss of catalytic residue at I97 (P = 0.0205);
MVP		0.18
MPC		0.38
ClinPred		0.12	T
GERP RS		3.5
Varity_R		0.084
gMVP		0.062

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-49278718;