3-49241359-A-G

Position:

• chr3-49241359-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135197.2(IHO1):​c.365A>G​(p.Lys122Arg) 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. 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1935975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHO1	NM_001135197.2	c.365A>G	p.Lys122Arg	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.365A>G	p.Lys122Arg	missense_variant	4/8	2	NM_001135197.2	ENSP00000407837.2
IHO1	ENST00000296449.9	c.365A>G	p.Lys122Arg	missense_variant	6/10	1		ENSP00000296449.5
IHO1	ENST00000438782.5	c.365A>G	p.Lys122Arg	missense_variant	4/8	5		ENSP00000391788.1
IHO1	ENST00000366429.2	c.365A>G	p.Lys122Arg	missense_variant	4/5	2		ENSP00000403700.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 20, 2024

The c.365A>G (p.K122R) 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 365, causing the lysine (K) at amino acid position 122 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.77	.;T;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.077
Sift	Uncertain	0.028	D;D;D;D
Sift4G	Benign	0.075	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.26
MutPred		0.14		Loss of ubiquitination at K122 (P = 0.0283);Loss of ubiquitination at K122 (P = 0.0283);Loss of ubiquitination at K122 (P = 0.0283);Loss of ubiquitination at K122 (P = 0.0283);
MVP		0.22
MPC		0.75
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.045

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: chr3-49278792;