chr3-49241285-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.851
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]

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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=0.040331453).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IHO1NM_001135197.2 linkuse as main transcriptc.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
IHO1ENST00000452691.7 linkuse as main transcriptc.291A>G p.Ile97Met missense_variant 4/82 NM_001135197.2 ENSP00000407837.2 Q8IYA8-1
IHO1ENST00000296449.9 linkuse as main transcriptc.291A>G p.Ile97Met missense_variant 6/101 ENSP00000296449.5 Q8IYA8-1
IHO1ENST00000438782.5 linkuse as main transcriptc.291A>G p.Ile97Met missense_variant 4/85 ENSP00000391788.1 Q8IYA8-1
IHO1ENST00000366429.2 linkuse as main transcriptc.291A>G p.Ile97Met missense_variant 4/52 ENSP00000403700.1 Q8IYA8-3

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 12, 2024The 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; API