Genetic Variant IZUMO1R:p.Tyr44Cys (chr11-94305767-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001199206.4(IZUMO1R):c.131A>G(p.Tyr44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

IZUMO1R
NM_001199206.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Publications

0 publications found

Variant links:

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]

IZUMO1R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.07387644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IZUMO1R	NM_001199206.4 link	c.131A>G	p.Tyr44Cys	missense_variant	Exon 2 of 5	ENST00000687084.1	NP_001186135.1	A6ND01-1
IZUMO1R	NM_001393610.1 link	c.131A>G	p.Tyr44Cys	missense_variant	Exon 1 of 4		NP_001380539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IZUMO1R	ENST00000687084.1 link	c.131A>G	p.Tyr44Cys	missense_variant	Exon 2 of 5		NM_001199206.4	ENSP00000510041.1	A6ND01-1
IZUMO1R	ENST00000328458.6 link	c.131A>G	p.Tyr44Cys	missense_variant	Exon 1 of 4	5		ENSP00000332963.5	A6ND01-1
IZUMO1R	ENST00000440961.6 link	c.131A>G	p.Tyr44Cys	missense_variant	Exon 1 of 4	5		ENSP00000416935.2	A6ND01-2

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000995

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:

0.000482

GnomAD2 exomes

AF:

0.0000926

AC:

AN:

248502

AF XY:

0.0000668

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461372

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726954

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111668

Other (OTH)

AF:

0.0000331

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000277

AC:

AN:

151634

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74064

show subpopulations

African (AFR)

AF:

0.000992

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67884

Other (OTH)

AF:

0.000477

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.000989

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.131A>G (p.Y44C) alteration is located in exon 1 (coding exon 1) of the IZUMO1R gene. This alteration results from a A to G substitution at nucleotide position 131, causing the tyrosine (Y) at amino acid position 44 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.089

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.66

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.9

M;M

PhyloP100

3.3

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.7

.;D

REVEL

Benign

0.27

Sift

Uncertain

0.0090

.;D

Sift4G

Uncertain

0.013

.;D

Polyphen

1.0

.;D

Vest4

0.53

MVP

0.31

MPC

0.17

ClinPred

0.25

GERP RS

3.3

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.38

gMVP

0.80

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr11-94305767-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over