chr11-94306544-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001199206.4(IZUMO1R):​c.170C>T​(p.Thr57Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T57N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IZUMO1R
NM_001199206.4 missense

Scores

3
13
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.49

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IZUMO1RNM_001199206.4 linkc.170C>T p.Thr57Ile missense_variant Exon 3 of 5 ENST00000687084.1 NP_001186135.1 A6ND01-1
IZUMO1RNM_001393610.1 linkc.170C>T p.Thr57Ile missense_variant Exon 2 of 4 NP_001380539.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IZUMO1RENST00000687084.1 linkc.170C>T p.Thr57Ile missense_variant Exon 3 of 5 NM_001199206.4 ENSP00000510041.1 A6ND01-1
IZUMO1RENST00000328458.6 linkc.170C>T p.Thr57Ile missense_variant Exon 2 of 4 5 ENSP00000332963.5 A6ND01-1
IZUMO1RENST00000440961.6 linkc.170C>T p.Thr57Ile missense_variant Exon 2 of 4 5 ENSP00000416935.2 A6ND01-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461682
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727128
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53390
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111852
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000241
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Uncertain
0.060
T
BayesDel_noAF
Uncertain
0.030
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.052
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.26
D
MutationAssessor
Pathogenic
3.3
M;M
PhyloP100
4.5
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-4.5
.;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0060
.;D
Sift4G
Uncertain
0.017
.;D
Polyphen
1.0
.;D
Vest4
0.78
MVP
0.56
MPC
0.17
ClinPred
0.90
D
GERP RS
4.8
Varity_R
0.66
gMVP
0.87
Mutation Taster
=44/56
disease causing

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

Other links and lift over

dbSNP: rs370423934; hg19: chr11-94039710; API