3-49256282-C-T

Variant names:

• chr3-49256282-C-T
• rs2046820621
• NM_001135197.2:c.785C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135197.2(IHO1):​c.785C>T​(p.Ser262Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IHO1 NM_001135197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.424
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059926808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IHO1	NM_001135197.2	MANE Select	c.785C>T	p.Ser262Leu	missense	Exon 8 of 8	NP_001128669.1	Q8IYA8-1
	IHO1	NM_178173.4		c.785C>T	p.Ser262Leu	missense	Exon 10 of 10	NP_835467.2	Q8IYA8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IHO1	ENST00000452691.7	TSL:2 MANE Select	c.785C>T	p.Ser262Leu	missense	Exon 8 of 8	ENSP00000407837.2	Q8IYA8-1
	IHO1	ENST00000296449.9	TSL:1	c.785C>T	p.Ser262Leu	missense	Exon 10 of 10	ENSP00000296449.5	Q8IYA8-1
	IHO1	ENST00000438782.5	TSL:5	c.785C>T	p.Ser262Leu	missense	Exon 8 of 8	ENSP00000391788.1	Q8IYA8-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.42
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.014
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.094
MutPred		0.29		Loss of disorder (P = 0.0496)
MVP		0.068
MPC		0.21
ClinPred		0.055	T
GERP RS		0.37
Varity_R		0.11
gMVP		0.21
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs2046820621; hg19: chr3-49293715;