Variant 3-49256521-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001135197.2(IHO1):c.1024C>T(p.His342Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

IHO1
NM_001135197.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.550

Variant links:

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]

IHO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.049786657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHO1	NM_001135197.2 linkuse as main transcript	c.1024C>T	p.His342Tyr	missense_variant	8/8	ENST00000452691.7	NP_001128669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IHO1	ENST00000452691.7 linkuse as main transcript	c.1024C>T	p.His342Tyr	missense_variant	8/8	2	NM_001135197.2	ENSP00000407837.2	Q8IYA8-1
IHO1	ENST00000296449.9 linkuse as main transcript	c.1024C>T	p.His342Tyr	missense_variant	10/10	1		ENSP00000296449.5	Q8IYA8-1
IHO1	ENST00000438782.5 linkuse as main transcript	c.1024C>T	p.His342Tyr	missense_variant	8/8	5		ENSP00000391788.1	Q8IYA8-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000239

AC:

AN:

251432

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000140

AC:

205

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000125

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.1024C>T (p.H342Y) 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 1024, causing the histidine (H) at amino acid position 342 to be replaced by a tyrosine (Y). 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

0.092

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.73

DANN

Benign

0.83

DEOGEN2

Benign

0.047

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.39

.;T;.

M_CAP

Benign

0.0059

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.064

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.67

P;P;P

Vest4

0.14

MVP

0.17

MPC

0.54

ClinPred

0.087

GERP RS

-4.8

Varity_R

0.060

gMVP

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over