chr3-49256176-C-T

Variant names:

• chr3-49256176-C-T
• rs1360119382
• NM_001135197.2:c.679C>T

Variant summary

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

The NM_001135197.2(IHO1):​c.679C>T​(p.Leu227Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IHO1 NM_001135197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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=0.18130869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IHO1	NM_001135197.2	c.679C>T	p.Leu227Phe	missense_variant	Exon 8 of 8	ENST00000452691.7	NP_001128669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IHO1	ENST00000452691.7	c.679C>T	p.Leu227Phe	missense_variant	Exon 8 of 8	2	NM_001135197.2	ENSP00000407837.2
IHO1	ENST00000296449.9	c.679C>T	p.Leu227Phe	missense_variant	Exon 10 of 10	1		ENSP00000296449.5
IHO1	ENST00000438782.5	c.679C>T	p.Leu227Phe	missense_variant	Exon 8 of 8	5		ENSP00000391788.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.679C>T (p.L227F) alteration is located in exon 10 (coding exon 7) of the CCDC36 gene. This alteration results from a C to T substitution at nucleotide position 679, causing the leucine (L) at amino acid position 227 to be replaced by a phenylalanine (F). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;T;T
Eigen	Benign	0.043
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.61	.;T;.
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.52	P;P;P
Vest4		0.26
MutPred		0.20		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.58
MPC		0.48
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.74
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs1360119382; hg19: chr3-49293609;