chr11-94307241-A-C

Position:

• chr11-94307241-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001199206.4(IZUMO1R):​c.425A>C​(p.Asp142Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000046 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000046 (0 hom., cov: 32)
• Consequence: IZUMO1R NM_001199206.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.82

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IZUMO1R	NM_001199206.4	c.425A>C	p.Asp142Ala	missense_variant	4/5	ENST00000687084.1
IZUMO1R	NM_001393610.1	c.425A>C	p.Asp142Ala	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IZUMO1R	ENST00000687084.1	c.425A>C	p.Asp142Ala	missense_variant	4/5		NM_001199206.4
IZUMO1R	ENST00000328458.6	c.425A>C	p.Asp142Ala	missense_variant	3/4	5
IZUMO1R	ENST00000440961.6	c.404A>C	p.Asp135Ala	missense_variant	3/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.69
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.0033
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.43	T
Polyphen		0.28	.;B
Vest4		0.57
MVP		0.49
MPC		0.061
ClinPred		0.70	D
GERP RS		3.5
Varity_R		0.17
gMVP		0.93

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

LitVar

Other links and lift over

dbSNP: rs933950417; hg19: chr11-94040407;