rs943950966

Variant names:

• chr11-94305746-C-G
• rs943950966
• NM_001199206.4:c.110C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-94305746-C-G
• chr11-94305746-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001199206.4(IZUMO1R):​c.110C>G​(p.Pro37Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P37L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: IZUMO1R NM_001199206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.99

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IZUMO1R	NM_001199206.4	c.110C>G	p.Pro37Arg	missense_variant	Exon 2 of 5	ENST00000687084.1	NP_001186135.1
IZUMO1R	NM_001393610.1	c.110C>G	p.Pro37Arg	missense_variant	Exon 1 of 4		NP_001380539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IZUMO1R	ENST00000687084.1	c.110C>G	p.Pro37Arg	missense_variant	Exon 2 of 5		NM_001199206.4	ENSP00000510041.1
IZUMO1R	ENST00000328458.6	c.110C>G	p.Pro37Arg	missense_variant	Exon 1 of 4	5		ENSP00000332963.5
IZUMO1R	ENST00000440961.6	c.110C>G	p.Pro37Arg	missense_variant	Exon 1 of 4	5		ENSP00000416935.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.6	H;H
PhyloP100		6.8
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-8.6	.;D
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		1.0	.;D
Vest4		0.94
MutPred		0.86		Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);
MVP		0.50
MPC		0.18
ClinPred		1.0	D
GERP RS		4.7
PromoterAI		0.038	Neutral
Varity_R		0.71
gMVP		0.91
Mutation Taster		=53/47	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: rs943950966; hg19: chr11-94038912;