Variant 3-49241388-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001135197.2(IHO1):c.394A>G(p.Ser132Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000503 in 1,608,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 1 hom. )

Consequence

IHO1
NM_001135197.2 missense, splice_region

Scores

Splicing: ADA: 0.9904

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHO1	NM_001135197.2 linkuse as main transcript	c.394A>G	p.Ser132Gly	missense_variant, splice_region_variant	4/8	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.394A>G	p.Ser132Gly	missense_variant, splice_region_variant	4/8	2	NM_001135197.2	ENSP00000407837.2	Q8IYA8-1
IHO1	ENST00000296449.9 linkuse as main transcript	c.394A>G	p.Ser132Gly	missense_variant, splice_region_variant	6/10	1		ENSP00000296449.5	Q8IYA8-1
IHO1	ENST00000438782.5 linkuse as main transcript	c.394A>G	p.Ser132Gly	missense_variant, splice_region_variant	4/8	5		ENSP00000391788.1	Q8IYA8-1
IHO1	ENST00000366429.2 linkuse as main transcript	c.394A>G	p.Ser132Gly	missense_variant, splice_region_variant	4/5	2		ENSP00000403700.1	Q8IYA8-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

245126

Hom.:

AF XY:

0.000181

AC XY:

AN XY:

132716

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:

0.000959

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000535

AC:

AN:

1456752

Hom.:

Cov.:

AF XY:

0.0000800

AC XY:

AN XY:

724606

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:

0.000786

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

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

Nov 20, 2023

The c.394A>G (p.S132G) 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 394, causing the serine (S) at amino acid position 132 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.60

.;T;.;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.085

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Benign

0.096

Sift

Uncertain

0.021

D;D;D;D

Sift4G

Uncertain

0.060

T;T;T;D

Polyphen

0.99

D;D;D;P

Vest4

0.39

MutPred

0.19

Gain of glycosylation at Y136 (P = 0.0043);Gain of glycosylation at Y136 (P = 0.0043);Gain of glycosylation at Y136 (P = 0.0043);Gain of glycosylation at Y136 (P = 0.0043);

MVP

0.34

MPC

0.54

ClinPred

0.41

GERP RS

4.8

Varity_R

0.30

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.90

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