rs537002321

Variant names:

• chr3-49256498-C-G
• rs537002321
• NM_001135197.2:c.1001C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-49256498-C-G
• chr3-49256498-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135197.2(IHO1):​c.1001C>G​(p.Ala334Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A334V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: IHO1 NM_001135197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16567984).

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.1001C>G	p.Ala334Gly	missense	Exon 8 of 8	NP_001128669.1	Q8IYA8-1
	IHO1	NM_178173.4		c.1001C>G	p.Ala334Gly	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.1001C>G	p.Ala334Gly	missense	Exon 8 of 8	ENSP00000407837.2	Q8IYA8-1
	IHO1	ENST00000296449.9	TSL:1	c.1001C>G	p.Ala334Gly	missense	Exon 10 of 10	ENSP00000296449.5	Q8IYA8-1
	IHO1	ENST00000438782.5	TSL:5	c.1001C>G	p.Ala334Gly	missense	Exon 8 of 8	ENSP00000391788.1	Q8IYA8-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.70
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.086
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.047	D
Polyphen		0.93	P
Vest4		0.15
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.51
MPC		0.80
ClinPred		0.94	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.059
Mutation Taster		=92/8	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: rs537002321; hg19: chr3-49293931;