NM_001199206.4:c.430C>G

Variant names:

• chr11-94307246-C-G
• rs776768539
• NM_001199206.4:c.430C>G

Variant summary

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

The NM_001199206.4(IZUMO1R):​c.430C>G​(p.Arg144Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R144C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IZUMO1R NM_001199206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848
• Publications: 3 publications found

Genes affected

IZUMO1R (HGNC:32565): (IZUMO1 receptor, JUNO) Enables signaling receptor activity. Predicted to be involved in cell adhesion; fusion of sperm to egg plasma membrane involved in single fertilization; and sperm-egg recognition. Predicted to be located in extracellular region and plasma membrane. Predicted to be anchored component of external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IZUMO1R	NM_001199206.4	c.430C>G	p.Arg144Gly	missense_variant	Exon 4 of 5	ENST00000687084.1	NP_001186135.1
IZUMO1R	NM_001393610.1	c.430C>G	p.Arg144Gly	missense_variant	Exon 3 of 4		NP_001380539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IZUMO1R	ENST00000687084.1	c.430C>G	p.Arg144Gly	missense_variant	Exon 4 of 5		NM_001199206.4	ENSP00000510041.1
IZUMO1R	ENST00000328458.6	c.430C>G	p.Arg144Gly	missense_variant	Exon 3 of 4	5		ENSP00000332963.5
IZUMO1R	ENST00000440961.6	c.409C>G	p.Arg137Gly	missense_variant	Exon 3 of 4	5		ENSP00000416935.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.1	M;.
PhyloP100		0.85
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.4	.;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0090	.;D
Polyphen		0.87	.;P
Vest4		0.36
MutPred		0.56		.;Loss of MoRF binding (P = 0.04);
MVP		0.52
MPC		0.094
ClinPred		0.98	D
GERP RS		-1.7
Varity_R		0.19
gMVP		0.74
Mutation Taster		=69/31	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: rs776768539; hg19: chr11-94040412;